請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87385完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 謝俊結 | zh_TW |
| dc.contributor.advisor | Jiun-Jie Shie | en |
| dc.contributor.author | 李治 | zh_TW |
| dc.contributor.author | Niaz Wali | en |
| dc.date.accessioned | 2023-05-19T08:46:38Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-07-19 | - |
| dc.date.issued | 2022 | - |
| dc.date.submitted | 2023-03-30 | - |
| dc.identifier.citation | Ch. 1
1.14 References 1. Jun, Joomyung V., David M. Chenoweth, and E. James Petersson. “Rational design of small molecule fluorescent probes for biological applications.” Organic & biomolecular chemistry 18.30 (2020): 5747-5763. 2. Lavis, Luke D., and Ronald T. Raines. “Bright building blocks for chemical biology.” ACS chemical biology 9.4 (2014): 855-866. 3. Grimm, Jonathan B., and Luke D. Lavis. “Caveat fluorophore: an insiders’ guide to small-molecule fluorescent labels.” Nature Methods 19.2 (2022): 149-158. 4. Zheng, Qinsi, Anthony X. Ayala, Inhee Chung, Aubrey V. Weigel, Anand Ranjan, Natalie Falco, Jonathan B. Grimm et al. "Rational design of fluorogenic and spontaneously blinking labels for super-resolution imaging." ACS Central Science 5, no. 9 (2019): 1602-1613. 5. Staderini, Matteo, María Antonia Martín, Maria Laura Bolognesi, and J. Carlos Menéndez. "Imaging of β-amyloid plaques by near infrared fluorescent tracers: a new frontier for chemical neuroscience." Chemical Society Reviews 44, no. 7 (2015): 1807-1819. 6. Alamudi, Samira Husen, and Young-Tae Chang. “Advances in the design of cell-permeable fluorescent probes for applications in live cell imaging.” Chemical Communications 54.97 (2018): 13641-13653. 7. Shaner, Nathan C., Paul A. Steinbach, and Roger Y. Tsien. “A guide to choosing fluorescent proteins.” Nature methods 2.12 (2005): 905-909. 8. Fu, Yanhua, and Nathaniel S. Finney. “Small-molecule fluorescent probes and their design.” RSC advances 8.51 (2018): 29051-29061. 9. Kubitscheck, Ulrich, ed. Fluorescence microscopy: from principles to biological applications. John Wiley & Sons, 2017. 10. Resch-Genger, Ute, Markus Grabolle, Sara Cavaliere-Jaricot, Roland Nitschke, and Thomas Nann. "Quantum dots versus organic dyes as fluorescent labels." Nature methods 5, no. 9 (2008): 763-775. 11. Grimm, Jonathan B., Laurel M. Heckman, and Luke D. Lavis. “The chemistry of small-molecule fluorogenic probes.” Progress in molecular biology and translational science 113 (2013): 1-34. 12. Specht, Elizabeth A., Esther Braselmann, and Amy E. Palmer. “A critical and comparative review of fluorescent tools for live-cell imaging.” Annual review of physiology 79 (2017): 93-117. 13. Wu, Luling, Chusen Huang, Ben P. Emery, Adam C. Sedgwick, Steven D. Bull, Xiao-Peng He, He Tian, Juyoung Yoon, Jonathan L. Sessler, and Tony D. James. "Förster resonance energy transfer (FRET)-based small-molecule sensors and imaging agents." Chemical Society Reviews 49, no. 15 (2020): 5110-5139. 14. Wu, Di, Adam C. Sedgwick, Thorfinnur Gunnlaugsson, Engin U. Akkaya, Juyoung Yoon, and Tony D. James. "Fluorescent chemosensors: the past, present and future." Chemical Society Reviews 46, no. 23 (2017): 7105-7123. 15. Daly, Brian, Jue Ling, and A. Prasanna De Silva. “Current developments in fluorescent PET (photoinduced electron transfer) sensors and switches.” Chemical Society Reviews 44.13 (2015): 4203-4211. 16. Wu, Jiasheng, Bomi Kwon, Weimin Liu, Eric V. Anslyn, Pengfei Wang, and Jong Seung Kim. "Chromogenic/fluorogenic ensemble chemosensing systems." Chemical reviews 115, no. 15 (2015): 7893-7943. 17. Svechkarev, Denis, and Aaron M. Mohs. “Organic fluorescent dye-based nanomaterials: Advances in the rational design for imaging and sensing applications.” Current medicinal chemistry 26.21 (2019): 4042-4064. 18. Shaner, Nathan C., Paul A. Steinbach, and Roger Y. Tsien. “A guide to choosing fluorescent proteins.” Nature methods 2.12 (2005): 905-909. 19. Lavis, Luke D., and Ronald T. Raines. “Bright ideas for chemical biology.” ACS chemical biology 3.3 (2008): 142-155. 20. Terai, Takuya, and Tetsuo Nagano. “Small-molecule fluorophores and fluorescent probes for bioimaging.” Pflügers Archiv-European Journal of Physiology 465.3 (2013): 347-359. 21. Brancaleon, Lorenzo, Anthony J. Durkin, John H. Tu, Gregg Menaker, Jerome D. Fallon, and Nikiforos Kollias. "In vivo fluorescence spectroscopy of nonmelanoma skin cancer¶." Photochemistry and Photobiology 73, no. 2 (2001): 178-183. 22. Ballou, Byron, Lauren A. Ernst, and Alan S. Waggoner. “Fluorescence imaging of tumors in vivo.” Current medicinal chemistry 12.7 (2005): 795-805. 23. Spence, Michelle TZ, and Iain D. Johnson, eds. The molecular probes handbook: a guide to fluorescent probes and labeling technologies. Life Technologies Corporation, 2010. 24. Yuan, Lin, Weiying Lin, Yueting Yang, and Hua Chen. "A unique class of near-infrared functional fluorescent dyes with carboxylic-acid-modulated fluorescence ON/OFF switching: rational design, synthesis, optical properties, theoretical calculations, and applications for fluorescence imaging in living animals." Journal of the American Chemical Society 134, no. 2 (2012): 1200-1211. 25. Terai, Takuya, and Tetsuo Nagano. “Fluorescent probes for bioimaging applications.” Current opinion in chemical biology 12.5 (2008): 515-521. 26. Wysocki, Laura M., and Luke D. Lavis. “Advances in the chemistry of small molecule fluorescent probes.” Current opinion in chemical biology 15.6 (2011): 752-759. 27. Liu, Xiao, and Young-Tae Chang. “Fluorescent probe strategy for live cell distinction.” Chemical Society Reviews (2022). 28. Fu, Yanhua, and Nathaniel S. Finney. “Small-molecule fluorescent probes and their design.” RSC advances 8.51 (2018): 29051-29061. 29. Turro, Nicholas J., Vaidhyanathan Ramamurthy, Vaidhyanathan Ramamurthy, and Juan C. Scaiano. Principles of molecular photochemistry: an introduction. University science books, 2009.; b. Lakowicz, Joseph R. “Principles of fluorescence spectroscopy Kluwer.” New York 23 (1999): 13261-13276; c. Montalti, Marco, et al. Handbook of photochemistry. CRC press, 2006; d. Klessinger, M., & Michl, J. (1995). Excited states and photochemistry of organic molecules. VCH publishers. 30. B. F. Herman, V. E. Centonze, J. R. Lakowicz, D. B. Murphy, K. R. Spring and M. W. Davidson, Basic Concepts in Fluorescence, https://micro.magnet.fsu.edu/primer/techniques/fluorescence/fluorescenceintro.html, (accessed Dec., 2022). 31. Myochin, Takuya, Kazuki Kiyose, Kenjiro Hanaoka, Hirotatsu Kojima, Takuya Terai, and Tetsuo Nagano. "Rational design of ratiometric near-infrared fluorescent pH probes with various p K a values, based on aminocyanine." Journal of the American Chemical Society 133, no. 10 (2011): 3401-3409. 32. Herschel, John Frederick William. “IV.’ Aμóρϕωτa, no. I.—on a case of superficial color presented by a homogeneous liquid internally colorless.” Philosophical Transactions of the Royal Society of London 135 (1845): 143-145. 33. Stokes, George Gabriel. “XXX. On the change of refrangibility of light.” Philosophical transactions of the Royal Society of London 142 (1852): 463-562. 34. Heim, Roger. “Improved green fluorescence.” Nature 373 (1995): 663-664. 35. Chalfie, Martin. “GFP: Lighting up life.” Proceedings of the National Academy of Sciences 106.25 (2009): 10073-10080. 36. Shimomura, Osamu. “Discovery of green fluorescent protein (GFP)(Nobel Lecture).” Angewandte Chemie International Edition 48.31 (2009): 5590-5602. 37. Chalfie, Martin, Yuan Tu, Ghia Euskirchen, William W. Ward, and Douglas C. Prasher. "Green fluorescent protein as a marker for gene expression." Science 263, no. 5148 (1994): 802-805. 38. Zimmer, Marc. “GFP: from jellyfish to the Nobel prize and beyond.” Chemical Society Reviews 38.10 (2009): 2823-2832. 39. Hell, Stefan W. “Toward fluorescence nanoscopy.” Nature biotechnology 21.11 (2003): 1347-1355. 40. Moerner, William E. “Nobel Lecture: Single-molecule spectroscopy, imaging, and photocontrol: Foundations for superresolution microscopy.” Reviews of Modern Physics 87.4 (2015). 41. Lippincott-Schwartz, Jennifer. “Profile of Eric Betzig, Stefan Hell, and WE Moerner, 2014 Nobel Laureates in Chemistry.” Proceedings of the National Academy of Sciences 112.9 (2015): 2630-2632. 42. Tipirneni, K. E., E. L. Rosenthal, L. S. Moore, A. D. Haskins, N. Udayakumar, A. H. Jani, W. R. Carroll et al. "Fluorescence imaging for cancer screening and surveillance." Molecular imaging and biology 19 (2017): 645-655. 43. Jewett, John C., and Carolyn R. Bertozzi. “Cu-free click cycloaddition reactions in chemical biology.” Chemical Society Reviews 39.4 (2010): 1272-1279. 44. McKay, Craig S., and M. G. Finn. “Click chemistry in complex mixtures: bioorthogonal bioconjugation.” Chemistry & biology 21.9 (2014): 1075-1101. 45. Patterson, David M., and Jennifer A. Prescher. “Orthogonal bioorthogonal chemistries.” Current opinion in chemical biology 28 (2015): 141-149. 46. Hang, Howard C., Chong Yu, Darryl L. Kato, and Carolyn R. Bertozzi. "A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation." Proceedings of the National Academy of Sciences 100, no. 25 (2003): 14846-14851. 47. Bertozzi, Carolyn R. “A decade of bioorthogonal chemistry.” Accounts of chemical research 44.9 (2011): 651-653. 48. Oliveira, B. L., Z. Guo, and G. J. L. Bernardes. “Inverse electron demand Diels–Alder reactions in chemical biology.” Chemical Society Reviews 46.16 (2017): 4895-4950. 49. Yamaguchi, Yoshihiro, Yoshio Matsubara, Takanori Ochi, Tateaki Wakamiya, and Zen-ichi Yoshida. "How the π conjugation length affects the fluorescence emission efficiency." Journal of the American Chemical Society 130, no. 42 (2008): 13867-13869. 50. Hanson, Kenneth, Luke Roskop, Peter I. Djurovich, Federico Zahariev, Mark S. Gordon, and Mark E. Thompson. "A paradigm for blue-or red-shifted absorption of small molecules depending on the site of π-extension." Journal of the American Chemical Society 132, no. 45 (2010): 16247-16255. 51. Valeur, Bernard, and M. N. Berberan-Santos. “Fluorescence microscopy.” Molecular Fluorescence, Second Edi. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany (2012): 327-348. 52. Hermanson, Greg T. Bioconjugate techniques. Academic press, 2013. 53. Grimm, Jonathan B., Ariana N. Tkachuk, Liangqi Xie, Heejun Choi, Boaz Mohar, Natalie Falco, Kathy Schaefer et al. "A general method to optimize and functionalize red-shifted rhodamine dyes." Nature methods 17, no. 8 (2020): 815-821. 54. Solov'ev, Konstantin N., and Elena A. Borisevich. “Intramolecular heavy-atom effect in the photophysics of organic molecules.” Physics-Uspekhi 48.3 (2005): 231. 55. Pauli, Jutta, Markus Grabolle, Robert Brehm, Monika Spieles, Franziska M. Hamann, Matthias Wenzel, Ingrid Hilger, and Ute Resch-Genger. "Suitable labels for molecular imaging–influence of dye structure and hydrophilicity on the spectroscopic properties of IgG conjugates." Bioconjugate chemistry 22, no. 7 (2011): 1298-1308. 56. Grzybowski, Marek, Masayasu Taki, Keiji Kajiwara, and Shigehiro Yamaguchi. "Effects of Amino Group Substitution on the Photophysical Properties and Stability of Near‐Infrared Fluorescent P‐Rhodamines." Chemistry–A European Journal 26, no. 35 (2020): 7912-7917. 57. Lei, Zuhai, Xinran Li, Xiao Luo, Haihong He, Jing Zheng, Xuhong Qian, and Youjun Yang. "Bright, stable, and biocompatible organic fluorophores absorbing/emitting in the deep near‐infrared spectral region." Angewandte Chemie International Edition 56, no. 11 (2017): 2979-2983. 58. Carlson, Jonathan CT, Labros G. Meimetis, Scott A. Hilderbrand, and Ralph Weissleder. "BODIPY–tetrazine derivatives as superbright bioorthogonal turn‐on probes." Angewandte Chemie international edition 52, no. 27 (2013): 6917-6920. 59. Properties of BODIPY for Bioimaging via meso-Amino Acylation.” Organic Letters (2022). 60. Lee, Uisung, Tae‐Il Kim, Sungjin Jeon, Yongyang Luo, Siyoung Cho, Jeehyeon Bae, and Youngmi Kim. "Native Chemical Ligation‐Based Fluorescent Probes for Cysteine and Aminopeptidase N Using meso‐thioester‐BODIPY." Chemistry–A European Journal 27, no. 49 (2021): 12545-12551. 61. Grimm, Jonathan B., Andrew J. Sung, Wesley R. Legant, Phuson Hulamm, Sylwia M. Matlosz, Eric Betzig, and Luke D. Lavis. "Carbofluoresceins and carborhodamines as scaffolds for high-contrast fluorogenic probes." ACS chemical biology 8, no. 6 (2013): 1303-1310. 62. Würth, Christian, Markus Grabolle, Jutta Pauli, Monika Spieles, and Ute Resch-Genger. "Relative and absolute determination of fluorescence quantum yields of transparent samples." Nature protocols 8, no. 8 (2013): 1535-1550. 63. Würth, Christian, Daniel Geißler, Thomas Behnke, Martin Kaiser, and Ute Resch-Genger. "Critical review of the determination of photoluminescence quantum yields of luminescent reporters." Analytical and bioanalytical chemistry 407 (2015): 59-78. 64. Carter, Kyle P., Alexandra M. Young, and Amy E. Palmer. “Fluorescent sensors for measuring metal ions in living systems.” Chemical reviews 114.8 (2014): 4564-4601. 65. Berezin, Mikhail Y., and Samuel Achilefu. “Fluorescence lifetime measurements and biological imaging.” Chemical reviews 110.5 (2010): 2641-2684. 66. Srinivasarao, Madduri, and Philip S. Low. “Ligand-targeted drug delivery.” Chemical reviews 117.19 (2017): 12133-12164. 67. Srinivasarao, Madduri, Chris V. Galliford, and Philip S. Low. “Principles in the design of ligand-targeted cancer therapeutics and imaging agents.” Nature reviews Drug discovery 14.3 (2015): 203-219. 68. Wang, Zhimin, and Bengang Xing. “Near‐Infrared Multipurpose Lanthanide‐Imaging Nanoprobes.” Chemistry–An Asian Journal 15.14 (2020): 2076-2091. 69. Lacivita, E., M. Leopoldo, F. Berardi, N. A Colabufo, and R. Perrone. "Activatable fluorescent probes: a new concept in optical molecular imaging." Current medicinal chemistry 19, no. 28 (2012): 4731-4741. 70. Kolanowski, Jacek L., Fei Liu, and Elizabeth J. New. “Fluorescent probes for the simultaneous detection of multiple analytes in biology.” Chemical Society Reviews 47.1 (2018): 195-208. 71. Stennett, Elana MS, Monika A. Ciuba, and Marcia Levitus. “Photophysical processes in single molecule organic fluorescent probes.” Chemical Society Reviews 43.4 (2014): 1057-1075. 72. Kako, Masahiro, and Yasuhiro Nakadaira. “Charge transfer complexes and electron transfer reaction of organosilicon and related compounds.” Coordination chemistry reviews 176.1 (1998): 87-112. 73. Wang, Zhimin, and Bengang Xing. “Small-molecule fluorescent probes: big future for specific bacterial labeling and infection detection.” Chemical Communications 58.2 (2022): 155-170. 74. Zhang, Wei, Zhao Ma, Lupei Du, and Minyong Li. "Design strategy for photoinduced electron transfer-based small-molecule fluorescent probes of biomacromolecules." Analyst 139, no. 11 (2014): 2641-2649. 75. de Silva, A. Prasanna, David B. Fox, Thomas S. Moody, and Sheenagh M. Weir. "The development of molecular fluorescent switches." TRENDS in Biotechnology 19, no. 1 (2001): 29-34. 76. Sparano, Brian A., and Kazunori Koide. “Fluorescent sensors for specific RNA: a general paradigm using chemistry and combinatorial biology.” Journal of the American Chemical Society 129.15 (2007): 4785-4794. 77. Szaciłowski, Konrad, Wojciech Macyk, Agnieszka Drzewiecka-Matuszek, Małgorzata Brindell, and Grażyna Stochel. "Bioinorganic photochemistry: frontiers and mechanisms." Chemical reviews 105, no. 6 (2005): 2647-2694. 78. De Silva, A. Prasanna, David B. Fox, Allen JM Huxley, and Thomas S. Moody. "Combining luminescence, coordination and electron transfer for signalling purposes." Coordination Chemistry Reviews 205, no. 1 (2000): 41-57. 79. Yang, Yuming, Qiang Zhao, Wei Feng, and Fuyou Li. "Luminescent chemodosimeters for bioimaging." Chemical Reviews 113, no. 1 (2013): 192-270. 80. Tanaka, Kumi, Tetsuo Miura, Naoki Umezawa, Yasuteru Urano, Kazuya Kikuchi, Tsunehiko Higuchi, and Tetsuo Nagano. "Rational design of fluorescein-based fluorescence probes. Mechanism-based design of a maximum fluorescence probe for singlet oxygen." Journal of the American Chemical Society 123, no. 11 (2001): 2530-2536. 81. Kim, Jong Seung, and Duong Tuan Quang. “Calixarene-derived fluorescent probes.” Chemical Reviews 107.9 (2007): 3780-3799. 82. Urano, Yasuteru, Mako Kamiya, Kojiro Kanda, Tasuku Ueno, Kenzo Hirose, and Tetsuo Nagano. "Evolution of fluorescein as a platform for finely tunable fluorescence probes." Journal of the American Chemical Society 127, no. 13 (2005): 4888-4894. 83. Yuan, Lin, Weiying Lin, Kaibo Zheng, and Sasa Zhu. "FRET-based small-molecule fluorescent probes: rational design and bioimaging applications." Accounts of chemical research 46, no. 7 (2013): 1462-1473. 84. Kikuchi, Kazuya, Hideo Takakusa, and Tetsuo Nagano. “Recent advances in the design of small molecule-based FRET sensors for cell biology.” TrAC Trends in Analytical Chemistry 23.6 (2004): 407-415. 85. Sapsford, Kim E., Lorenzo Berti, and Igor L. Medintz. “Materials for fluorescence resonance energy transfer analysis: beyond traditional donor–acceptor combinations.” Angewandte Chemie International Edition 45.28 (2006): 4562-4589. 86. Zhang, Xiaolin, Yi Xiao, and Xuhong Qian. “A ratiometric fluorescent probe based on FRET for imaging Hg2+ ions in living cells.” Angewandte Chemie 120.42 (2008): 8145-8149. 87. Grimm, Jonathan B., Ariana N. Tkachuk, Heejun Choi, Boaz Mohar, Natalie Falco, Ronak Patel, Jennifer Lippincott-Schwartz, Timothy A. Brown, and Luke D. Lavis. "Optimization and functionalization of red-shifted rhodamine dyes." bioRxiv (2019): 2019-12. 88. Bassolino, Giovanni, Christoph Nançoz, Zacharias Thiel, Estelle Bois, Eric Vauthey, and Pablo Rivera-Fuentes. "Photolabile coumarins with improved efficiency through azetidinyl substitution." Chemical Science 9, no. 2 (2018): 387-391. 89. Sarmah, Manashi, Kangkana Chutia, Dhiraj Dutta, and Pranjal Gogoi. "Overview of coumarin-fused-coumarins: synthesis, photophysical properties and their applications." Organic & Biomolecular Chemistry 20, no. 1 (2022): 55-72. 90. Ajay Kumar, K., N. Renuka, G. Pavithra, and G. Vasanth. "Comprehensive review on coumarins: Molecules of potential chemical and pharmacological interest." Journal of Chemical and Pharmaceutical research 7, no. 9 (2015): 67-81. 91. Duke, Rebecca M., Emma B. Veale, Frederick M. Pfeffer, Paul E. Kruger, and Thorfinnur Gunnlaugsson. "Colorimetric and fluorescent anion sensors: an overview of recent developments in the use of 1, 8-naphthalimide-based chemosensors." Chemical society reviews 39, no. 10 (2010): 3936-3953. 92. Beija, Mariana, Carlos AM Afonso, and José MG Martinho. “Synthesis and applications of Rhodamine derivatives as fluorescent probes.” Chemical Society Reviews 38.8 (2009): 2410-2433. 93. Duan, Yousheng, Ming Liu, Wei Sun, Min Wang, Shangzhong Liu, and Qing X. Li. "Recent progress on synthesis of fluorescein probes." Mini-Reviews in Organic Chemistry 6, no. 1 (2009): 35-43. 94. Shindy, H. A. “Fundamentals in the chemistry of cyanine dyes: A review.” Dyes and Pigments 145 (2017): 505-513. 95. Gopika, G. S., PM Hari Prasad, A. G. Lekshmi, S. Lekshmypriya, S. Sreesaila, C. Arunima, Malavika S. Kumar, Arathy Anil, Anjana Sreekumar, and Zeena S. Pillai. "Chemistry of cyanine dyes-A review." Materials Today: Proceedings 46 (2021): 3102-3108. 96. Loudet, Aurore, and Kevin Burgess. “BODIPY dyes and their derivatives: syntheses and spectroscopic properties.” Chemical reviews 107.11 (2007): 4891-4932. 97. Ulrich, Gilles, Raymond Ziessel, and Anthony Harriman. “The chemistry of fluorescent bodipy dyes: versatility unsurpassed.” Angewandte Chemie International Edition 47.7 (2008): 1184-1201. 98. Guo, Zhiqian, Sookil Park, Juyoung Yoon, and Injae Shin. "Recent progress in the development of near-infrared fluorescent probes for bioimaging applications." Chemical Society Reviews 43, no. 1 (2014): 16-29. 99. Lu, Hua, John Mack, Yongchao Yang, and Zhen Shen. "Structural modification strategies for the rational design of red/NIR region BODIPYs." Chemical Society Reviews 43, no. 13 (2014): 4778-4823. 100. Guo, Zhiqian, Sookil Park, Juyoung Yoon, and Injae Shin. "Recent progress in the development of near-infrared fluorescent probes for bioimaging applications." Chemical Society Reviews 43, no. 1 (2014): 16-29. 101. Banuelos, Jorge. “BODIPY dye, the most versatile fluorophore ever?.” The Chemical Record 16.1 (2016): 335-348. 102. Ziessel, Raymond, Gilles Ulrich, and Anthony Harriman. “The chemistry of Bodipy: A new El Dorado for fluorescence tools.” New Journal of Chemistry 31.4 (2007): 496-501. 103. Benstead, Michael, Georg H. Mehl, and Ross W. Boyle. “4, 4'-Difluoro-4-bora-3a, 4a-diaza-s-indacenes (BODIPYs) as components of novel light active materials.” Tetrahedron (Oxford. Print) 67.20 (2011). 104. Bumagina, Natalia A., Elena V. Antina, Alexander A. Ksenofontov, Lubov A. Antina, Alexander A. Kalyagin, and Mikhail B. Berezin. "Basic structural modifications for improving the practical properties of BODIPY." Coordination Chemistry Reviews 469 (2022): 214684. 105. Sunahara, Hisato, Yasuteru Urano, Hirotatsu Kojima, and Tetsuo Nagano. "Design and synthesis of a library of BODIPY-based environmental polarity sensors utilizing photoinduced electron-transfer-controlled fluorescence ON/OFF switching." Journal of the American Chemical Society 129, no. 17 (2007): 5597-5604. 106. Qian, Xuhong, Yi Xiao, Yufang Xu, Xiangfeng Guo, Junhong Qian, and Weipin Zhu. "“Alive” dyes as fluorescent sensors: fluorophore, mechanism, receptor and images in living cells." Chemical Communications 46, no. 35 (2010): 6418-6436. 107. Boens, Noël, Volker Leen, and Wim Dehaen. “Fluorescent indicators based on BODIPY.” Chemical Society Reviews 41.3 (2012): 1130-1172. 108. Kritskaya, Anna Yu, Natalia A. Bumagina, Elena V. Antina, Alexander A. Ksenofontov, Mikhail B. Berezin, and Alexander S. Semeikin. "Synthesis and Photochemical Properties of 2, 3; 5, 6-bis (cyclohexano)-BODIPY." Journal of Fluorescence 28 (2018): 393-407. 109. Lu, Jia‐sheng, Huiying Fu, Yanguang Zhang, Zygmunt J. Jakubek, Ye Tao, and Suning Wang. "A dual emissive BODIPY dye and its use in functionalizing highly monodispersed PbS nanoparticles." Angewandte Chemie 123, no. 49 (2011): 11862-11866. 110. Sun, Changxia, Jinghe Yang, Lei Li, Xia Wu, Yang Liu, and Shufang Liu. "Advances in the study of luminescence probes for proteins." Journal of chromatography B 803, no. 2 (2004): 173-190. 111. Umezawa, Keitaro, Daniel Citterio, and Koji Suzuki. “New trends in near-infrared fluorophores for bioimaging.” Analytical Sciences 30.3 (2014): 327-349. 112. Kue, Chin Siang, Shie Yin Ng, Siew Hui Voon, Anyanee Kamkaew, Lip Yong Chung, Lik Voon Kiew, and Hong Boon Lee. "Recent strategies to improve boron dipyrromethene (BODIPY) for photodynamic cancer therapy: an updated review." Photochemical & Photobiological Sciences 17 (2018): 1691-1708. 113. Umezawa, Keitaro, Akihiro Matsui, Yuki Nakamura, Daniel Citterio, and Koji Suzuki. "Bright, color‐tunable fluorescent dyes in the Vis/NIR region: establishment of new “tailor‐made” multicolor fluorophores based on borondipyrromethene." Chemistry–A European Journal 15, no. 5 (2009): 1096-1106. 114. Lu, Hua, John Mack, Yongchao Yang, and Zhen Shen. "Structural modification strategies for the rational design of red/NIR region BODIPYs." Chemical Society Reviews 43, no. 13 (2014): 4778-4823. 115. Dolušić, Eduard, H. Thien Ngo, Wouter Maes, and Wim Dehaen. "Efficient synthesis of aryldipyrromethanes in water and their application in the synthesis of corroles and dipyrromethenes." Arkivoc 10 (2007): 307-324. 116. Shah, Mayur, Kannappan Thangaraj, Mou‐Ling Soong, Lionel T. Wolford, Joseph H. Boyer, Ieva R. Politzer, and Theodore G. Pavlopoulos. "Pyrromethene–BF2 complexes as laser dyes: 1." Heteroatom Chemistry 1, no. 5 (1990): 389-399. 117. Boyer, Joseph H., Anthony M. Haag, Govindarao Sathyamoorthi, Mou‐Ling Soong, Kannappan Thangaraj, and Theodore G. Pavlopoulos. "Pyrromethene–BF2 complexes as laser dyes: 2." Heteroatom Chemistry 4, no. 1 (1993): 39-49. 118. Li, Zaiguo, Evan Mintzer, and Robert Bittman. “First synthesis of free cholesterol− BODIPY conjugates.” The Journal of organic chemistry 71.4 (2006): 1718-1721. 119. Ma, Chunyu, Shumin Hou, Xin Zhou, Zonghua Wang, and Juyoung Yoon. "Rational design of meso-phosphino-substituted BODIPY probes for imaging hypochlorite in living cells and mice." Analytical Chemistry 93, no. 27 (2021): 9640-9646. 120. Nguyen, Van‐Nghia, Yubin Yim, Sangin Kim, Bokyeong Ryu, K. M. K. Swamy, Gyoungmi Kim, Nahyun Kwon, C‐Yoon Kim, Sungnam Park, and Juyoung Yoon. "Molecular Design of Highly Efficient Heavy‐Atom‐Free Triplet BODIPY Derivatives for Photodynamic Therapy and Bioimaging." Angewandte Chemie International Edition 59, no. 23 (2020): 8957-8962. 121. Lv, Wen, Yafei Li, Feiyang Li, Xin Lan, Yaming Zhang, Lili Du, Qiang Zhao, David L. Phillips, and Weiping Wang. "Upconversion-like photolysis of BODIPY-based prodrugs via a one-photon process." Journal of the American Chemical Society 141, no. 44 (2019): 17482-17486. 122. Aguiar, Antonio, Joana Farinhas, Wanderson da Silva, Isabel C. Santos, Luis Alcacer, Christopher MA Brett, Jorge Morgado, and Abilio JFN Sobral. "New series of BODIPY dyes: Synthesis, characterization and applications in photovoltaic cells and light-emitting diodes." Dyes and Pigments 193 (2021): 109517. 123. De Wael, E. Vos, J. A. Pardoen, J. A. Van Koeveringe, and J. Lugtenburg. "Pyrromethene‐BF2 complexes (4, 4′‐difluoro‐4‐bora‐3a, 4a‐diaza‐s‐indacenes). Synthesis and luminescence properties." Recueil des Travaux Chimiques des Pays‐Bas 96, no. 12 (1977): 306-309. 124. Ksenofontov, Alexander A., Pavel S. Bocharov, Ksenia V. Ksenofontova, and Elena V. Antina. "Water-Soluble BODIPY-Based fluorescent probe for BSA and HSA detection." Journal of Molecular Liquids 345 (2022): 117031. 125. Wories, H. J., J. H. Koek, G. Lodder, J. Lugtenburg, R. Fokkens, O. Driessen, and G. R. Mohn. "A novel water‐soluble fluorescent probe: Synthesis, luminescence and biological properties of the sodium salt of the 4‐sulfonato‐3, 3′, 5, 5′‐tetramethyl‐2, 2′‐pyrromethen‐1, 1′‐BF2 complex." Recueil des Travaux Chimiques des Pays‐Bas 104, no. 11 (1985): 288-291. 126. Bañuelos, Jorge, Virginia Martín, CF Azael Gómez‐Durán, Ismael J. Arroyo Córdoba, Eduardo Peña‐Cabrera, Inmaculada García‐Moreno, Ángel Costela, M. Eugenia Pérez‐Ojeda, Teresa Arbeloa, and Íñigo López Arbeloa. "New 8‐Amino‐BODIPY derivatives: Surpassing laser dyes at blue‐edge wavelengths." Chemistry–A European Journal 17, no. 26 (2011): 7261-7270. 127. Guseva, Galina B., Alexander A. Ksenofontov, Elena V. Antina, Mikhail B. Berezin, and Anatoliy I. Vyugin. "Effect of solvent nature on spectral properties of blue-emitting meso-propargylamino-BODIPY." Journal of Molecular Liquids 285 (2019): 194-203. 128. Esnal, Ixone, Jorge Bañuelos, Iñigo López Arbeloa, Angel Costela, Inmaculada Garcia-Moreno, Miguel Garzón, Antonia R. Agarrabeitia, and María José Ortiz. "Nitro and amino BODIPYS: crucial substituents to modulate their photonic behavior." RsC Advances 3, no. 5 (2013): 1547-1556. 129. Cieślik-Boczula, Katarzyna, Kevin Burgess, Lingling Li, Binh Nguyen, Lesley Pandey, Wim M. De Borggraeve, Mark Van der Auweraer, and Noël Boens. "Photophysics and stability of cyano-substituted boradiazaindacene dyes." Photochemical & Photobiological Sciences 8 (2009): 1006-1015. 130. Yakubovskyi, Viktor P., Natalia O. Didukh, Yuriy V. Zatsikha, and Yuriy P. Kovtun. "A New Approach to the Synthesis of meso‐CN‐Substituted BODIPYs." ChemistrySelect 1, no. 7 (2016): 1462-1466. 131. Alamiry, Mohammed AH, Andrew C. Benniston, Jerry Hagon, Thomas PL Winstanley, Helge Lemmetyinen, and Nikolai V. Tkachenko. "The fluorine effect: photophysical properties of borondipyrromethene (bodipy) dyes appended at the meso position with fluorinated aryl groups." RSC advances 2, no. 11 (2012): 4944-4950. 132. Duran‐Sampedro, Gonzalo, Antonia R. Agarrabeitia, Inmaculada Garcia‐Moreno, Angel Costela, Jorge Bañuelos, Teresa Arbeloa, Inigo Lopez Arbeloa, Jose Luis Chiara, and María J. Ortiz. "Chlorinated BODIPYs: surprisingly efficient and highly photostable laser dyes." European Journal of Organic Chemistry 2012, no. 32 (2012): 6335-6350. 133. Lakshmi, V., and M. Ravikanth. “Brominated boron dipyrrins: synthesis, structure, spectral and electrochemical properties.” Dalton Transactions 41.19 (2012): 5903-5911. 134. Yogo, Takatoshi, Yasuteru Urano, Yukiko Ishitsuka, Fumio Maniwa, and Tetsuo Nagano. "Highly efficient and photostable photosensitizer based on BODIPY chromophore." Journal of the American Chemical Society 127, no. 35 (2005): 12162-12163. 135. Hedley, Gordon J., Arvydas Ruseckas, Anthony Harriman, and Ifor DW Samuel. "Conformational effects on the dynamics of internal conversion in boron dipyrromethene dyes in solution." Angewandte Chemie International Edition 50, no. 29 (2011): 6634-6637. 136. Kee, Hooi Ling, Christine Kirmaier, Lianhe Yu, Patchanita Thamyongkit, W. Justin Youngblood, Matthew E. Calder, Lavoisier Ramos et al. "Structural control of the photodynamics of boron− dipyrrin complexes." The journal of physical chemistry B 109, no. 43 (2005): 20433-20443. 137. Demchenko, Alexander P. “Photobleaching of organic fluorophores: quantitative characterization, mechanisms, protection.” Methods and Applications in Fluorescence 8.2 (2020): 022001. 138. Hinkeldey, Babette, Alexander Schmitt, and Gregor Jung. “Comparative photostability studies of BODIPY and fluorescein dyes by using fluorescence correlation spectroscopy.” ChemPhysChem 9.14 (2008): 2019-2027. 139. Cunha Dias de Rezende, Lucas, Miguel Menezes Vaidergorn, Juliana Cristina Biazzotto Moraes, and Flavio da Silva Emery. "Synthesis, photophysical properties and solvatochromism of meso-substituted tetramethyl BODIPY dyes." Journal of fluorescence 24 (2014): 257-266. 140. Wang, Jun, Qinghua Wu, Changjiang Yu, Yun Wei, Xiaolong Mu, Erhong Hao, and Lijuan Jiao. "Aromatic ring fused BOPHYs as stable red fluorescent dyes." The Journal of Organic Chemistry 81, no. 22 (2016): 11316-11323. 141. Courtis, Alexandra M., Sofia A. Santos, Yinghua Guan, J. Adam Hendricks, Balaram Ghosh, D. Miklos Szantai-Kis, Surya A. Reis, Jagesh V. Shah, and Ralph Mazitschek. "Monoalkoxy BODIPYs A Fluorophore Class for Bioimaging." Bioconjugate chemistry 25, no. 6 (2014): 1043-1051. 142. Martynov, Vladimir I., and Alexey A. Pakhomov. “BODIPY derivatives as fluorescent reporters of molecular activities in living cells.” Russian Chemical Reviews 90.10 (2021): 1213. 143. Molecular Probes.1 HandbookÐA Guide to Fluorescent Probes and Labeling Technologies (Online Version). Ch. 12; https://www.thermofisher.com/ru/ru/home/global/forms/mp-handbook-download-request-form-2014.html (Last access 15.12.2022) 144. Kand, Dnyaneshwar, Lorena Pizarro, Inbar Angel, Adi Avni, Dinorah Friedmann‐Morvinski, and Roy Weinstain. "Organelle‐Targeted BODIPY Photocages: Visible‐Light‐Mediated Subcellular Photorelease." Angewandte Chemie International Edition 58, no. 14 (2019): 4659-4663. 145. López-Duarte, Ismael, Thanh Truc Vu, M. Angeles Izquierdo, James A. Bull, and Marina K. Kuimova. "A molecular rotor for measuring viscosity in plasma membranes of live cells." Chemical Communications 50, no. 40 (2014): 5282-5284. 146. Bardon, Kevin M., Scott Selfridge, Dany S. Adams, Richard A. Minns, Robert Pawle, Timothy C. Adams, and Larry Takiff. "Synthesis of water-soluble far-red-emitting amphiphilic BODIPY dyes." ACS omega 3, no. 10 (2018): 13195-13199. 147. Cavazos‐Elizondo, Daniela, and Alan Aguirre‐Soto. “Photophysical Properties of Fluorescent Labels: A Meta‐Analysis to Guide Probe Selection Amidst Challenges with Available Data.” Analysis & Sensing 2.5 (2022): e202200004. 148. Li, Chenge, Alison G. Tebo, and Arnaud Gautier. “Fluorogenic labeling strategies for biological imaging.” International Journal of Molecular Sciences 18.7 (2017): 1473. 149. Schreiber, Cynthia L., and Bradley D. Smith. "Molecular conjugation using noncovalent click chemistry." Nature Reviews Chemistry 3.6 (2019): 393-400. 150. Brea, Roberto J., and Neal K. Devaraj. “Diels–Alder and Inverse Diels–Alder Reactions.” Chemoselective and Bioorthogonal Ligation Reactions: Concepts and Applications 1 (2017): 67-95. 151. Algar, W. Russ, Philip Dawson, and Igor L. Medintz, eds. “Chemoselective and bioorthogonal ligation reactions: concepts and applications.” (2017). 152. Nanda, Jagpreet S., and Jon R. Lorsch. “Labeling a protein with fluorophores using NHS ester derivitization.” Methods Enzymol 536 (2014): 87-94. 153. Narain, Ravin, ed. Chemistry of bioconjugates: synthesis, characterization, and biomedical applications. John Wiley & Sons, 2013. 154. Barbarella, Giovanna, Massimo Zambianchi, Alfredo Ventola, Eduardo Fabiano, Fabio Della Sala, Giuseppe Gigli, Marco Anni et al. "Bright oligothiophene N-succinimidyl esters for efficient fluorescent labeling of proteins and oligonucleotides." Bioconjugate chemistry 17, no. 1 (2006): 58-67. 155. Renault, Kévin, Jean Wilfried Fredy, Pierre-Yves Renard, and Cyrille Sabot. "Covalent modification of biomolecules through maleimide-based labeling strategies." Bioconjugate Chemistry 29, no. 8 (2018): 2497-2513. 156. Nanda, Jagpreet S., and Jon R. Lorsch. “Labeling of a protein with fluorophores using maleimide derivitization.” Methods Enzymol 536 (2014): 79-86. 157. Riederer, Irène M., Rosario Moreno Herrero, Geneviève Leuba, and Beat M. Riederer. "Serial protein labeling with infrared maleimide dyes to identify cysteine modifications." Journal of proteomics 71, no. 2 (2008): 222-230. Chapter 2. 1. Jewett, John C., and Carolyn R. Bertozzi. "Cu-free click cycloaddition reactions in chemical biology." Chemical Society Reviews 39.4 (2010): 1272-1279. 2. McKay, Craig S., and M. G. Finn. "Click chemistry in complex mixtures: bioorthogonal bioconjugation." Chemistry & biology 21.9 (2014): 1075-1101. 3. Patterson, David M., and Jennifer A. Prescher. "Orthogonal bioorthogonal chemistries." Current opinion in chemical biology 28 (2015): 141-149. 4. Hang, Howard C., et al. "A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation." Proceedings of the National Academy of Sciences 100.25 (2003): 14846-14851. 5. Bertozzi, Carolyn R. "A decade of bioorthogonal chemistry." Accounts of chemical research 44.9 (2011): 651-653. 6. Oliveira, B. L., Z. Guo, and G. J. L. Bernardes. "Inverse electron demand Diels–Alder reactions in chemical biology." Chemical Society Reviews 46.16 (2017): 4895-4950. B). Fan, Xinyuan, Jie Li, and Peng R. Chen. "Bioorthogonal chemistry in living animals." National Science Review 4, no. 3 (2017): 300-302. 7. Wieczorek, Achim, et al. "Green-to far-red-emitting fluorogenic tetrazine probes–synthetic access and no-wash protein imaging inside living cells." Chemical science 8.2 (2017): 1506-1510. 8. Carlson, Jonathan CT, et al. "BODIPY–tetrazine derivatives as superbright bioorthogonal turn‐on probes." Angewandte Chemie international edition 52.27 (2013): 6917-6920. 9. Devaraj, Neal K., et al. "Bioorthogonal turn‐on probes for imaging small molecules inside living cells." Angewandte Chemie 122.16 (2010): 2931-2934. 10. Carlson, Jonathan CT, et al. "BODIPY–tetrazine derivatives as superbright bioorthogonal turn‐on probes." Angewandte Chemie international edition 52.27 (2013): 6917-6920. 11. Meimetis, Labros G., et al. "Ultrafluorogenic coumarin–tetrazine probes for real‐time biological imaging." Angewandte Chemie 126.29 (2014): 7661-7664. 12. Wu, Haoxing, et al. "In situ synthesis of alkenyl tetrazines for highly fluorogenic bioorthogonal live‐cell imaging probes." Angewandte Chemie 126.23 (2014): 5915-5919. 13. Haiber, Lisa Maria, Markus Kufleitner, and Valentin Wittmann. "Application of the Inverse-Electron-Demand Diels-Alder Reaction for Metabolic Glycoengineering." Frontiers in Chemistry 9 (2021): 654932. 14. Parle, Daniel R., et al. "Metabolic Glycan Labeling of Cancer Cells Using Variably Acetylated Monosaccharides." Bioconjugate Chemistry 33.8 (2022): 1467-1473. 15. (Agramunt, Jordi, et al. "Inverse Electron-Demand Diels–Alder Bioconjugation Reactions Using 7-Oxanorbornenes as Dienophiles." The Journal of Organic Chemistry 85.10 (2020): 6593-6604. 16. Wu, Chien-Chi, et al. "Flexible Construction Approach to the Synthesis of 1, 5-Substituted Pyrrole-3-carbaldehydes from 5-Bromo-1, 2, 3-triazine." Organic Letters 24.15 (2022): 2889-2893. Chapter 3: 3.6 References 1. Siegel RL, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64. 2. Riihimaki M, et al. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765. 3. Price TJ. Advanced colorectal cancer treatment options beyond standard systemic therapy. Lancet Oncol. 2017;18(2):157–9. 4. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352(5):476–87. 5. Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020;5(1):22. 6. Nan Y, Wu C, Zhang YJ. Interplay between janus kinase/signal transducer and activator of transcription signaling activated by type I interferons and viral antagonism. Front Immunol. 2017;8:1758. 7. Mertens C, et al. Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N‑terminal domain. Genes Dev. 2006;20(24):3372–81. 8. Murray PJ. The JAK‑STAT signaling pathway: input and output integration. J Immunol. 2007;178(5):2623–9. 9. Zou S, et al. Targeting STAT3 in cancer immunotherapy. Mol Cancer. 2020;19(1):145. 10. Thilakasiri PS, et al. Repurposing of drugs as STAT3 inhibitors for cancer therapy. Semin Cancer Biol. 2021;68:31–46. 11. Platanias LC. Mechanisms of type‑I‑ and type‑II‑interferon‑mediated signaling. Nat Rev Immunol. 2005;5(5):375–86. 12. Loh CY, et al. Signal transducer and activator of transcription (STATs) pro‑ teins in cancer and inflammation: functions and therapeutic implication. Front Oncol. 2019;9:48. 13. Khodarev NN, Roizman B, Weichselbaum RR. Molecular pathways: inter‑ feron/stat1 pathway: role in the tumor resistance to genotoxic stress and aggressive growth. Clin Cancer Res. 2012;18(11):3015–21. 14. Avalle L, et al. STAT1 and STAT3 in tumorigenesis: a matter of balance. JAKSTAT. 2012;1(2):65–72. 15. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798–809. 16. Hix LM, et al. Tumor STAT1 transcription factor activity enhances breast tumor growth and immune suppression mediated by myeloid‑derived suppressor cells. J Biol Chem. 2013;288(17):11676–88. 17. Greenwood C, et al. Stat1 and CD74 overexpression is co‑dependent and linked to increased invasion and lymph node metastasis in triple‑negative breast cancer. J Proteomics. 2012;75(10):3031–40. 18. Zimmerman MA, et al. Unphosphorylated STAT1 promotes sarcoma development through repressing expression of Fas and bad and confer‑ ring apoptotic resistance. Cancer Res. 2012;72(18):4724–32. 19. Meissl K, et al. The good and the bad faces of STAT1 in solid tumors. Cytokine. 2017;89:12–20. 20. Keseru GM, Makara GM. The influence of lead discovery strategies on the properties of drug candidates. Nat Rev Drug Discov. 2009;8(3):203–12. 21. Yan XC, et al. Augmenting hit identification by virtual screening techniques in small molecule drug discovery. J Chem Inf Model. 2020;60(9):4144–52. 22. Lin H. The computational methods in drug targets discovery. Curr Drug Targets. 2019;20(5):479–80. 23. Maia EHB, et al. Structure‑based virtual screening: from classical to artifi‑ cial intelligence. Front Chem. 2020;8:343. 24. Banegas‑Luna AJ, Ceron‑Carrasco JP, Perez‑Sanchez H. A review of ligand‑based virtual screening web tools and screening algorithms in large molecular databases in the age of big data. Future Med Chem. 2018;10(22):2641–58. 25. Vazquez J, et al. Merging ligand‑based and structure‑based methods in drug discovery: an overview of combined virtual screening approaches. Molecules. 2020. https://doi.org/10.3390/molecules25204723. 26. Gao M, et al. Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy. Chem Soc Rev. 2017;46(8):2237–71. 27. Garland M, Yim JJ, Bogyo M. A bright future for precision medicine: advances in fluorescent chemical probe design and their clinical application. Cell Chem Biol. 2016;23(1):122–36. 28. Wei TT, et al. Dual targeting of 3‑hydroxy‑3‑methylglutaryl coenzyme a reductase and histone deacetylase as a therapy for colorectal cancer. EBioMedicine. 2016;10:124–36. 29. Kumar A, Zhang KYJ. Advances in the development of shape similarity methods and their application in drug discovery. Front Chem. 2018;6:315. 30. Baris S, et al. Severe early‑onset combined immunodeficiency due to heterozygous gain‑of‑function mutations in STAT1. J Clin Immunol. 2016;36(7):641–8. 31. Luo CK, et al. Cannabinoids orchestrate cross‑talk between cancer cells and endothelial cells in colorectal cancer. Cancer Gene Ther. 2021. https://doi.org/10.1038/s41417‑021‑00346‑0. 32. Xu D, Qu CK. Protein tyrosine phosphatases in the JAK/STAT pathway. Front Biosci. 2008;13:4925–32. 33. Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol. 2008;26(17):2839–45. 34. Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res. 2012;22(3):457–72. 35. Munro MJ, et al. Cancer stem cells in colorectal cancer: a review. J Clin Pathol. 2018;71(2):110–6. 36. De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumor angiogenesis. Nat Rev Cancer. 2017;17(8):457–74. 37. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3(6):401–10. 38. Zhang X, et al. STAT1 inhibits miR‑181a expression to suppress colorectal cancer cell proliferation through PTEN/Akt. J Cell Biochem. 2017;118(10):3435–43. 39. Stempelj M, et al. Essential role of the JAK/STAT1 signaling pathway in the expression of inducible nitric‑oxide synthase in intestinal epithelial cells and its regulation by butyrate. J Biol Chem. 2007;282(13):9797–804. 40. Kaler P, et al. The role of STAT1 for crosstalk between fibroblasts and colon cancer cells. Front Oncol. 2014;4:88. 41. Niu M, et al. Upregulation of STAT1‑CCL5 axis is a biomarker of colon cancer and promotes the proliferation of colon cancer cells. Ann Transl Med. 2020;8(15):951. 42. Wang S, et al. STAT1 promotes KRAS colon tumor growth and susceptibility to pharmacological inhibition of translation initiation factor eIF4A. Mol Cancer Ther. 2016;15(12):3055–63. 43. Qadir AS, et al. CD95/Fas increases stemness in cancer cells by inducing a STAT1‑dependent type I interferon response. Cell Rep. 2017;18(10):2373–86. 44. Malilas W, et al. Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation. Int J Oncol. 2013;43(4):1111–6. 45. Le Bon A, Tough DF. Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol. 2002;14(4):432–6. 46. Takeda A, et al. Cutting edge: role of IL‑27/WSX‑1 signaling for induction of T‑bet through activation of STAT1 during initial Th1 commitment. J Immunol. 2003;170(10):4886–90. 47. Chen TT, et al. STAT1 regulates marginal zone B-cell differentiation in response to inflammation and infection with blood‑borne bacteria. J Exp Med. 2016;213(13):3025–39. 48. Darnell JE Jr, Kerr IM, Stark GR. Jak‑STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994;264(5164):415–21. 49. Bradfute SB, et al. A STAT‑1 knockout mouse model for Machupo virus pathogenesis. Virol J. 2011;8:300. 50. Villarino AV, Gallo E, Abbas AK. STAT1‑activating cytokines limit Th17 responses through both T‑bet‑dependent and ‑independent mechanisms. J Immunol. 2010;185(11):6461–71. 51. Popivanova BK, et al. Blocking TNF‑alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest. 2008;118(2):560–70. 52. Gordon S, Pluddemann A, Martinez Estrada F. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014;262(1):36–55. 53. Bain CC, Schridde A. Origin, differentiation, and function of intestinal macrophages. Front Immunol. 2018;9:2733. 54. Gu Y, Mohammad IS, Liu Z. Overview of the STAT‑3 signaling path‑ way in cancer and the development of specific inhibitors. Oncol Lett. 2020;19(4):2585–94. 55. Yang L, et al. Novel activators and small‑molecule inhibitors of STAT3 in cancer. Cytokine Growth Factor Rev. 2019;49:10–22. 56. Bharadwaj U, et al. Targeting janus kinases and signal transducer and activator of transcription 3 to treat inflammation, fibrosis, and cancer: rationale, progress, and caution. Pharmacol Rev. 2020;72(2):486–526. 57. Verhoeven Y, et al. The potential and controversy of targeting STAT family members in cancer. Semin Cancer Biol. 2020;60:41–56. 58. Schwartz DM, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;17(1):78. 59. Hammaren HM, et al. The regulation of JAKs in cytokine signaling and its breakdown in disease. Cytokine. 2019;118:48–63. 60. Gupta S, et al. The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN‑alpha signals. EMBO J. 1996;15(5):1075–84. 61. Schneider M, et al. The PROTACtable genome. Nat Rev Drug Discov. 2021;20(10):789–97. 62. Reynders M, et al. PHOTACs enable optical control of protein degradation. Sci Adv. 2020;6(8):eaay5064. 63. Bai L, et al. A potent and selective small‑molecule degrader of STAT3 achieves complete tumor regression in vivo. Cancer Cell. 2019;36(5):498‑ 511 e17. 64. Zhou H, et al. Structure‑based discovery of SD‑36 as a potent, selective, and efficacious PROTAC degrader of STAT3 protein. J Med Chem. 2019;62(24):11280–300. 65. Lavis LD, Raines RT. Bright building blocks for chemical biology. ACS Chem Biol. 2014;9(4):855–66. 66. Gong YJ, et al. A unique approach toward near‑infrared fluorescent probes for bioimaging with markedly enhanced contrast. Chem Sci. 2016;7(3):2275–85. 67. Deng P, et al. A novel BODIPY quaternary ammonium salt‑based fluorescent probe: synthesis, physical properties, and live‑cell imaging. Front Chem. 2021;9: 650006. 68. Gupta N, et al. A bodipy based fluorescent probe for evaluating and identifying cancer, normal and apoptotic C6 cells on the basis of changes in intracellular viscosity. J Mater Chem B. 2016;4(11):1968–77. 69. Madibone KS, et al. Cyclic organoselenide BODIPY-based probe: targeting superoxide in MCF-7 cancer cells. ACS Omega. 2020;5(23):14186–93. 70. Martin C, et al. The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumor models. Br J Cancer. 2003;89(8):1581–9. 71. Jagodinsky JC, et al. Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs. J Biol Inorg Chem. 2015;20(7):1081–95. 72. Badowski ME, Yanful PK. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Ther Clin Risk Manag. 2018;14:643–51. 73. Qiu T, et al. Exploring the mechanism of flavonoids through systematic bioinformatics analysis. Front Pharmacol. 2018;9:918. 74. Mbachu OC, et al. SAR study on estrogen receptor alpha/beta activity of (iso)flavonoids: importance of prenylation, c-ring (un)saturation, and hydroxyl substituents. J Agric Food Chem. 2020;68(39):10651–63. 75. Bode AM, Dong Z. Signal transduction and molecular targets of selected flavonoids. Antioxid Redox Signal. 2013;19(2):163–80. 76. Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019;47(W1):W357–64. 77. Yu Y, et al. Soy isoflavone consumption and colorectal cancer risk: a systematic review and meta-analysis. Sci Rep. 2016;6:25939. 78. Wang Q, et al. Soy isoflavone: the multipurpose phytochemical (review). Biomed Rep. 2013;1(5):697–701. 79. Munro IC, et al. Soy isoflavones: a safety review. Nat. Rev. 2003;61(1):1–33. Chapter 4. 4.5 References 1. Piazza, Pier Vincenzo, and Michel Le Moal. “Glucocorticoids as a biological substrate of reward: physiological and pathophysiological implications.” Brain Research Reviews 25.3 (1997): 359-372. 2. De Kloet, E. Ron, Marian Joëls, and Florian Holsboer. “Stress and the brain: from adaptation to disease.” Nature reviews neuroscience 6.6 (2005): 463-475. 3. McEwen, Bruce S., and Peter J. Gianaros. “Stress-and allostasis-induced brain plasticity.” Annual review of medicine 62 (2011): 431. 4. Sandi, Carmen. “Stress, cognitive impairment and cell adhesion molecules.” Nature Reviews Neuroscience 5.12 (2004): 917-930. 5. Vallée, Monique, Sergio Vitiello, Luigi Bellocchio, Etienne Hébert-Chatelain, Stéphanie Monlezun, Elena Martin-Garcia, Fernando Kasanetz et al. "Pregnenolone can protect the brain from cannabis intoxication." science 343, no. 6166 (2014): 94-98. 6. Hiort, Olaf, Wiebke Birnbaum, Louise Marshall, Lutz Wünsch, Ralf Werner, Tatjana Schröder, Ulla Döhnert, and Paul-Martin Holterhus. "Management of disorders of sex development." Nature Reviews Endocrinology 10, no. 9 (2014): 520-529. 7. Musgrove, Elizabeth A., and Robert L. Sutherland. “Biological determinants of endocrine resistance in breast cancer.” Nature Reviews Cancer 9.9 (2009): 631-643. 8. Fenyvesi, Éva, István Puskás, and Lajos Szente. “Applications of steroid drugs entrapped in cyclodextrins.” Environmental Chemistry Letters 17.1 (2019): 375-391. 9. Weng, Jui-Hsia, and Bon-chu Chung. “Nongenomic actions of neurosteroid pregnenolone and its metabolites.” Steroids 111 (2016): 54-59. 10. Tong, Wang-Yu, and Xiang Dong. “Microbial biotransformation: recent developments on steroid drugs.” Recent patents on biotechnology 3.2 (2009): 141-153. 11. Fernández-Cabezón, Lorena, Beatriz Galán, and José L. García. "New insights on steroid biotechnology." Frontiers in microbiology 9 (2018): 958. 12. Joselevich, María, Alberto A. Ghini, and Gerardo Burton. “6, 19-Carbon-bridged steroids. Synthesis of 6, 19-methanoprogesterone.” Organic & biomolecular chemistry 1.6 (2003): 939-943. 13. Neves, AndréS Campos, Maria Luisa Sáe Melo, Maria JoséS M. Moreno, Elisiário J. Tavares da Silva, Jorge AR Salvador, Saul P. da Costa, and Rosa Maria LM Martins. "Improved syntheses of aromatase inhibitors and neuroactive steroids efficient oxidations and reductions at key positions for bioactivity." Tetrahedron 55, no. 11 (1999): 3255-3264. 14. Barredo, José-Luis, and Ignacio Herráiz, eds. Microbial steroids: Methods and protocols. Humana Press, 2017. 15. Mellon, Synthia H., and Lisa D. Griffin. “Neurosteroids: biochemistry and clinical significance.” Trends in endocrinology & metabolism 13.1 (2002): 35-43. 16. Schumacher, Martin, Sebastien Weill-Engerer, Philippe Liere, Francoise Robert, R. J. M. Franklin, Luis M. Garcia-Segura, Jeremy J. Lambert et al. "Steroid hormones and neurosteroids in normal and pathological aging of the nervous system." Progress in neurobiology 71, no. 1 (2003): 3-29. 17. Maggio, Marcello, Francesca De Vita, Alberto Fisichella, Elena Colizzi, Sandra Provenzano, Fulvio Lauretani, Michele Luci et al. "DHEA and cognitive function in the elderly." The Journal of steroid biochemistry and molecular biology 145 (2015): 281-292. 18. Strott, Charles A. “Sulfonation and molecular action.” Endocrine reviews 23.5 (2002): 703-732. 19. Baulieu, E. E., Pl Robel, and M. Schumacher. “Neurosteroids: beginning of the story.” International review of neurobiology 46 (2001): 1-32. 20. Vallée, Monique, Sergio Vitiello, Luigi Bellocchio, Etienne Hébert-Chatelain, Stéphanie Monlezun, Elena Martin-Garcia, Fernando Kasanetz et al. "Pregnenolone can protect the brain from cannabis intoxication." science 343, no. 6166 (2014): 94-98. 21. Huang, Sheng-Chieh, Cheng-tse Lee, and Bon-chu Chung. “Tumor necrosis factor suppresses NR5A2 activity and intestinal glucocorticoid synthesis to sustain chronic colitis.” Science Signaling 7.314 (2014): ra20-ra20. 22. Mellon, Synthia H., and Lisa D. Griffin. “Neurosteroids: biochemistry and clinical significance.” Trends in endocrinology & metabolism 13.1 (2002): 35-43. 23. Shih, Meng-Chun Monica, Yi-Ning Chiu, Meng-Chun Hu, Chern Guo, and Bon-chu Chung. "Regulation of steroid production: analysis of Cyp11a1 promoter." Molecular and Cellular Endocrinology 336, no. 1-2 (2011): 80-84. 24. Hu, Meng-Chun, Nai-Chi Hsu, Noomen Ben El Hadj, Chin-I. Pai, Hsueh-Ping Chu, Chi-Kuang Leo Wang, and Bon-chu Chung. "Steroid deficiency syndromes in mice with targeted disruption of Cyp11a1." Molecular endocrinology 16, no. 8 (2002): 1943-1950. 25. Jo, Do-Hyun, Malika Aït Abdallah, Jacques Young, Etienne-Emile Baulieu, and Paul Robel. "Pregnenolone, dehydroepiandrosterone, and their sulfate and fatty acid esters in the rat brain." Steroids 54, no. 3 (1989): 287-297. 26. Luchetti, S., I. S. D. F. Huitinga, and D. F. Swaab. “Neurosteroid and GABA-A receptor alterations in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis.” Neuroscience 191 (2011): 6-21. 27. Mahata, Bidesh, Xiuwei Zhang, Aleksandra A. Kolodziejczyk, Valentina Proserpio, Liora Haim-Vilmovsky, Angela E. Taylor, Daniel Hebenstreit et al. "Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis." Cell reports 7, no. 4 (2014): 1130-1142. 28. Stoffel-Wagner, Birgit. “Neurosteroid metabolism in the human brain.” European Journal of Endocrinology 145.6 (2001): 669-679. 29. Mellon, Synthia H., and Lisa D. Griffin. “Neurosteroids: biochemistry and clinical significance.” Trends in endocrinology & metabolism 13.1 (2002): 35-43. 30. Raux, Pierre‐louis, Guillaume Drutel, Jean‐michel Revest, and Monique Vallée. "New perspectives on the role of the neurosteroid pregnenolone as an endogenous regulator of type‐1 cannabinoid receptor (CB1R) activity and function." Journal of Neuroendocrinology 34, no. 2 (2022): e13034. 31. Lin, Yiqi Christina, Garett Cheung, Edith Porter, and Vassilios Papadopoulos. "The neurosteroid pregnenolone is synthesized by a mitochondrial P450 enzyme other than CYP11A1 in human glial cells." Journal of Biological Chemistry 298, no. 7 (2022). 32. Papadopoulos, V., L. Lecanu, R. C. Brown, Z. Han, and Z-X. Yao. "Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders." Neuroscience 138, no. 3 (2006): 749-756. 33. Payne, Anita H., and Dale B. Hales. “Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones.” Endocrine reviews 25.6 (2004): 947-970. 34. Rupprecht, Rainer, Christian H. Wetzel, Mario Dorostkar, Jochen Herms, Nathalie L. Albert, Jens Schwarzbach, Michael Schumacher, and Inga D. Neumann. "Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?." Molecular Psychiatry 27, no. 7 (2022): 2918-2926. 35. Witzig, Melissa, Amandine Grimm, Karen Schmitt, Imane Lejri, Stephan Frank, Steven A. Brown, and Anne Eckert. "Clock-controlled mitochondrial dynamics correlates with cyclic pregnenolone synthesis." Cells 9, no. 10 (2020): 2323. 36. Lin, Yiqi Christina, Garett Cheung, Nidia Espinoza, and Vassilios Papadopoulos. "Function, regulation, and pharmacological effects of pregnenolone in the central nervous system." Current Opinion in Endocrine and Metabolic Research 22 (2022): 100310. 37. H.J. Hsu, M.R. Liang, C.T. Chen, B.C. Chung, pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement, Nature 439 (2006) 480–483. 38. Weng, Jui-Hsia, et al. “Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration.” Nature chemical biology 9.10 (2013): 636-642. 39. Flood, James F., John E. Morley, and Eugene Roberts. “Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it.” Proceedings of the National Academy of Sciences 89.5 (1992): 1567-1571. 40. C.E. Marx, R.S. Keefe, R.W. Buchanan, R.M. Hamer, J.D. Kilts, D.W. Bradford, et al., Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia, Neuropsychopharmacology 34 (2009) 1885–1903. 41. M.S. Ritsner, A. Gibel, T. Shleifer, I. Boguslavsky, A. Zayed, R. Maayan, et al., pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial, J. Clin. Psychiatry 71(2010) 1351–1362. 42. S. Haraguchi, S. Hara, T. Ubuka, M. Mita, K. Tsutsui, Possible role of pineal allopregnanolone in Purkinje cell survival, Proc. Natl. Acad. Sci. U.S.A. 109 (2012) 21110–21115. 43. L.D. Griffin, W. Gong, L. Verot, S.H. Mellon, Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone, Nat. Med. 10 (2004) 704–711. 44. F. Noorbakhsh, G.B. Baker, C. Power, Allopregnanolone and neuroinflammation: a focus on multiple sclerosis, Front. Cell. Neurosci. 8 (2014) 134. 45. M. Vallee, W. Mayo, M. Darnaudery, C. Corpechot, J. Young, M. Koehl, et al., Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus, Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 14865–14870. 46. M. Vallee, W. Mayo, M. Le Moal, Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging, Brain Res. Brain Res. Rev. 37 (2001) 301–312. 47. S.C. Chen, B.C. Liu, C.W. Chen, F.S. Wu, Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in rats, Biochem. Biophys. Res. Commun. 349 (2006) 626–633. 48. M.D. Majewska, M.T. Bluet-Pajot, P. Robel, E.E. Baulieu, Pregnenolone sulfate antagonizes barbiturate-induced hypnosis, Pharmacol. Biochem. Behav. 33 (1989) 701–703. 49. J.L. Yau, J. Noble, M. Graham, J.R. Seckl, Central administration of a cytochrome P450–7B product 7 alpha-hydroxypregnenolone improves spatial memory retention in cognitively impaired aged rats, J. Neurosci. 26 (2006) 11034–11040. 50. Matsunaga, Masahiro, Kazuyoshi Ukena, Etienne-Emile Baulieu, and Kazuyoshi Tsutsui. "7α-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system." Proceedings of the National Academy of Sciences 101, no. 49 (2004): 17282-17287. 51. Tsutsui, Kazuyoshi, Kazuhiko Inoue, Hitomi Miyabara, Saori Suzuki, Yuki Ogura, and Shogo Haraguchi. "7α-Hydroxypregnenolone mediates melatonin action underlying diurnal locomotor rhythms." Journal of Neuroscience 28, no. 9 (2008): 2158-2167. 52. Chakraborty, Soura, Jhuma Pramanik, and Bidesh Mahata. “Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies.” Genes & Immunity 22.3 (2021): 125-140 53. Mitchison, Tim, and Marc Kirschner. “Dynamic instability of microtubule growth.” nature 312.5991 (1984): 237-242. 54. Barbiero, Isabella, Massimiliano Bianchi, and Charlotte Kilstrup‐Nielsen. “Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting.” Journal of Neuroendocrinology 34.2 (2022): e13033. 55. Murakami, Koichi, Arlette Fellous, Etienne-Emile Baulieu, and Paul Robel. "Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly." Proceedings of the National Academy of Sciences 97, no. 7 (2000): 3579-3584. 56. Drewes, Gerard, Andreas Ebneth, and Eva-Maria Mandelkow. “MAPs, MARKs and microtubule dynamics.” Trends in biochemical sciences 23.8 (1998): 307-311. 57. Fontaine-Lenoir, Virginie, Béatrice Chambraud, Arlette Fellous, Sébastien David, Yann Duchossoy, Etienne-Emile Baulieu, and Paul Robel. "Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor." Proceedings of the National Academy of Sciences 103, no. 12 (2006): 4711-4716. 58. Nakano, Atsushi, Hisakazu Kato, Takashi Watanabe, Kyung-Duk Min, Satoru Yamazaki, Yoshihiro Asano, Osamu Seguchi et al. "AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation." Nature cell biology 12, no. 6 (2010): 583-590. 59. Arnal, Isabelle, Claire Heichette, Georgios S. Diamantopoulos, and Denis Chrétien. "CLIP-170/tubulin-curved oligomers coassemble at microtubule ends and promote rescues." Current Biology 14, no. 23 (2004): 2086-2095. 60. Murugan, Subathra, Padmaja Jakka, Swapna Namani, Varadendra Mujumdar, and Girish Radhakrishnan. "The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation." Journal of Biological Chemistry 294, no. 12 (2019): 4596-4607. 61. M. Hamasaki, S. Matsumura, A. Satou, C. Takahashi, Y. Oda, C. Higashiura, et al.,Pregnenolone functions in centriole cohesion during mitosis, Chem. Biol. 21 (2014) 1707–1721. 62. Brown, Rachel C., Zeqiu Han, Caterina Cascio, and Vassilios Papadopoulos. "Oxidative stress-mediated DHEA formation in Alzheimer’s disease pathology." Neurobiology of aging 24, no. 1 (2003): 57-65. 63. Naylor, Jennifer C., Jason D. Kilts, Christine M. Hulette, David C. Steffens, Dan G. Blazer, John F. Ervin, Jennifer L. Strauss et al. "Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects." Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1801, no. 8 (2010): 951-959. 64. Weill-Engerer, Sébastien, Jean-Philippe David, Véronique Sazdovitch, Philippe Liere, Bernard Eychenne, Antoine Pianos, Michael Schumacher, André Delacourte, Etienne-Emile Baulieu, and Yvette Akwa. "Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients." The Journal of Clinical Endocrinology & Metabolism 87, no. 11 (2002): 5138-5143. 65. Naylor, Jennifer C., Christine M. Hulette, David C. Steffens, Lawrence J. Shampine, John F. Ervin, Victoria M. Payne, Mark W. Massing et al. "Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer’s disease, and related to neuropathological disease stage." The Journal of Clinical Endocrinology & Metabolism 93, no. 8 (2008): 3173-3178. 66. Kim, Sae-Bom, Martin Hill, Yong-Tae Kwak, Richard Hampl, Do-Hyun Jo, and Robert Morfin. "Neurosteroids: cerebrospinal fluid levels for Alzheimer’s disease and vascular dementia diagnostics." The Journal of Clinical Endocrinology & Metabolism 88, no. 11 (2003): 5199-5206. 67. Liu, Sha, Honghai Wu, Gai Xue, Xin Ma, Jie Wu, Yabin Qin, and Yanning Hou. "Metabolic alteration of neuroactive steroids and protective effect of progesterone in Alzheimer's disease-like rats." Neural regeneration research 8, no. 30 (2013): 2800. 68. Noorbakhsh, Farshid, Kristofor K. Ellestad, Ferdinand Maingat, Kenneth G. Warren, May H. Han, Lawrence Steinman, Glen B. Baker, and Christopher Power. "Impaired neurosteroid synthesis in multiple sclerosis." Brain 134, no. 9 (2011): 2703-2721. 69. Giatti, S., R. Rigolio, Silvia Diviccaro, E. Falvo, D. Caruso, Luis M. Garcia-Segura, G. Cavaletti, and R. C. Melcangi. "Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis." The Journal of Steroid Biochemistry and Molecular Biology 199 (2020): 105596. 70. Melcangi, Roberto Cosimo, Donatella Caruso, Giovanna Levandis, Federico Abbiati, Marie-Therese Armentero, and Fabio Blandini. "Modifications of neuroactive steroid levels in an experimental model of nigrostriatal degeneration: potential relevance to the pathophysiology of Parkinson’s disease." Journal of Molecular Neuroscience 46 (2012): 177-183. 71. Ritsner, Michael, Rachel Maayan, Anatoly Gibel, and Abraham Weizman. "Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects." European neuropsychopharmacology 17, no. 5 (2007): 358-365. 72. Marx, Christine E., Robert D. Stevens, Lawrence J. Shampine, Veska Uzunova, William T. Trost, Marian I. Butterfield, Mark W. Massing, Robert M. Hamer, A. Leslie Morrow, and Jeffrey A. Lieberman. "Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics." Neuropsychopharmacology 31, no. 6 (2006): 1249-1263. 73. George, Mark S., A. Guidotti, David Rubinow, Baishen Pan, Kirstin Mikalauskas, and Robert M. Post. "CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI." Biological Psychiatry 35, no. 10 (1994): 775-780. 74. Labombarda, F., A. Pianos, P. Liere, B. Eychenne, S. Gonzalez, A. Cambourg, Alejandro Federico De Nicola, Michael Schumacher, and Rachida Guennoun. "Injury elicited increase in spinal cord neurosteroid content analyzed by gas chromatography mass spectrometry." Endocrinology 147, no. 4 (2006): 1847-1859. 75. Patte-Mensah, Christine, Cherkaouia Kibaly, Domitille Boudard, Véronique Schaeffer, Aurélie Béglé, Simona Saredi, Laurence Meyer, and Ayikoe G. Mensah-Nyagan. "Neurogenic pain and steroid synthesis in the spinal cord." Journal of molecular neuroscience 28 (2006): 17-31. 76. Zhang, Meng, Jia Liu, Meng‐Meng Zhou, Honghai Wu, Yanning Hou, Yun‐Feng Li, Yuxin Yin et al. "Anxiolytic effects of hippocampal neurosteroids in normal and neuropathic rats with spared nerve injury." Journal of neurochemistry 141, no. 1 (2017): 137-150. 77. Zhang, Meng, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin et al. "Elevated neurosteroids in the lateral thalamus relieve neuropathic pain in rats with spared nerve injury." Neuroscience bulletin 32 (2016): 311-322. 78. M. Bianchi, E.E. Baulieu, 3beta-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders, Proc. Natl. Acad. Sci. U.S.A. 109 (2012) 1713–1718 79. A. Hidalgo, R.C. Suzano, M.P. Revuelta, C. Sanchez-Diaz, A. Baamonde, B. Cantabrana, Calcium and depolarization-dependent effect of pregnenolone derivatives on uterine smooth muscle, Gen. Pharmacol. 27 (1996) 879–885. 80. M. Iqbal Choudhary, M. Shahab Alam, R. Atta Ur, S. Yousuf, Y.C. Wu, A.S. Lin, et al., Pregnenolone derivatives as potential anticancer agents, Steroids 76 (2011) 1554–1559. 81. D.N. Grigoryev, B.J. Long, V.C. Njar, A.H. Brodie, Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor, J. Steroid Biochem. Mol. Biol. 75 (2000) 1–10. 82. Vallée, Monique. “Structure-activity relationship studies on neuroactive steroids in memory, alcohol and stress-related functions: a crucial benefit from endogenous level analysis.” Psychopharmacology 231.17 (2014): 3243-3255. 83. Vallee, M., W. Shen, S. C. Heinrichs, C. F. Zorumski, D. F. Covey, George F. Koob, and R. H. Purdy. "Steroid structure and pharmacological properties determine the anti‐amnesic effects of pregnenolone sulphate in the passive avoidance task in rats." European Journal of Neuroscience 14, no. 12 (2001): 2003-2010. 84. Bianchi, Massimiliano, and Etienne-Emile Baulieu. “3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders.” Proceedings of the National Academy of Sciences 109.5 (2012): 1713-1718. 85. Weissleder, Ralph, and Matthias Nahrendorf. “Advancing biomedical imaging.” Proceedings of the National Academy of Sciences 112.47 (2015): 14424-14428. 86. Zhang, Gong, Siqi Zheng, Haiping Liu, and Peng R. Chen. "Illuminating biological processes through site-specific protein labeling." Chemical Society Reviews 44, no. 11 (2015): 3405-3417. 87. Borrmann, Annika, and Jan CM van Hest. “Bioorthogonal chemistry in living organisms.” Chemical Science 5.6 (2014): 2123-2134. 88. E Rincon-Limas, Diego, Kurt Jensen, and Pedro Fernandez-Funez. “Drosophila models of proteinopathies: the little fly that could.” Current pharmaceutical design 18.8 (2012): 1108-1122. 89. Baranowski, Elizabeth S., Wiebke Arlt, and Jan Idkowiak. “Monogenic disorders of adrenal steroidogenesis.” Hormone research in pediatrics 89.5 (2018): 292-310 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87385 | - |
| dc.description.abstract | 神經甾體孕烯醇酮 (P5) 可促進神經微管聚合延伸，減輕與精神分裂症相關的壓力和負面症狀，促進記憶增強，並有助於恢復脊髓損傷。在類固醇生成過程中，孕烯醇酮是第一個從膽固醇中獲得的神經類固醇，它會迅速通過酶代謝轉化為下游類固醇家族成員。因此，很難區分 P5 與大腦中其他下游類固醇的生物活性。為了解決這個問題，在論文第一部分，我們合成並篩選了孕烯醇酮衍生物，通過修飾孕烯醇酮的 C-3、C-5、C-7 和 C-20 位置，希望延緩其代謝機制，同時測試了它們增強微管延伸和神經發育的能力。化合物 JJS-043 被發現是 P5 的有效類似物；它可增強微管聚合，穩定活細胞中的微管動力學，加速神經軸突生長，同時可改變了小鼠小腦顆粒神經元培養物中的生長錐形態。另一方面，它也可促進了斑馬魚小腦軸突中穩定微管軸突的形成。 與孕烯醇酮不同的是，化合物JJS-043不易被代謝，但在體內可維持與 P5 一樣功能活性，可被視為神經發育疾病的治療候選藥物。
結直腸癌 (CRC) 病例在全球範圍內不斷激增，迫切需要新藥來治療 CRC。Signal-transducer and activator of transcription-1 (STAT1) 在腫瘤發生中具有複雜的作用機制，其在 CRC 中的作用仍需深入了解。在論文第二部分，我們發現在 CRC 患者和小鼠模型中，降低 STAT1的磷酸化活性，可抑制腫瘤生長。基於配體的高通量篩選揭示了大豆中富含的大豆異黃酮化合物“金雀異黃酮”（THIF：4',5,7-三羥基異黃酮），是一種新的 STAT1 抑制劑。我們合成了基於 BODIPY 的金雀異黃酮螢光探針用以研究 THIF 和 STAT1 的抑制機制作用。 我們的研究顯示THIF 可阻止 STAT1-STAT1 二聚化，消除了 CRC 中的干性和血管生成，並且小鼠模型中的體內結果減弱了腫瘤生長。除此之外，我們也合成了基於金雀異黃酮的 PROTAC（靶向嵌合體的蛋白水解）降解劑，用以靶向 CRC 中的 STAT1 降解，此研究正持續進行中。 細胞表面的異常醣基化被認為是癌症的標誌之一。追踪此類醣基化途徑有助於了解腫瘤的進展、診斷和治療發展。在論文第三部分，我們採用聚醣代謝工程 (MOE) 來修飾聚醣，其中含有一種含有獨特烯烴標記的生物正交化學報告基團的非天然單醣前體，可用於聚醣代謝工程，並通過生物合成結合到活細胞的多醣中，藉由生物正交化學反應，可與 BODIPY 探針的互補生物正交四嗪官能團發生反應，進行共價螢光標定。我們設計的BODIPY是具有螢光發光性質的探針，發射範圍從綠色到紅色發射 BODIPY 骨架。我們目前的研究表明，這些探針是烯烴功能化單醣的特異性螢光標記試劑，可適用於通過共聚焦顯微鏡觀察細胞中烯烴標記的醣基化共軛物的定位及追蹤。 | zh_TW |
| dc.description.abstract | Neurosteroid pregnenolone (P5) promotes microtubule polymerization, alleviates stress and negative symptoms associated with schizophrenia, promotes memory enhancement, and helps recover spinal-cord injury. During steroidogenesis, pregnenolone is the first neurosteroid obtained from the cholesterol, and it quickly undergoes enzymatic conversion into the downstream steroids. Therefore, it is difficult to distinguish the biological activity of P5 versus other downstream steroids in the brain. To address this issue, we synthesized and screened pregnenolone derivatives to delay its further metabolism via modification at C-3, C-5, C-7, and C-20 positions and tested their ability to enhance microtubule elongation and neural development. Compound JJS-043 was found to be a potent analog of P5; it enhanced microtubule polymerization, stabilized microtubule dynamics in live cells, accelerated neurite growth, and changed the growth cone morphology in mouse cerebellar granule neuronal-culture. It also promoted the formation of stable microtubule tracks in cerebellar-axons of zebrafish. JJS-043, unlike pregnenolone, resist metabolism but recapitulates P5 functions in-vivo and can be considered a therapeutic candidate for neuro-developmental diseases.
Colorectal cancer (CRC) cases have a constant surge globally, and there is a urgent need for new medicines to treat CRC. Signal-transducer and activator of transcription-1 (STAT1) have a complex role in tumorigenesis, and its role in CRC still requires in-depth comprehension. As part of this work, an alleviated STAT1 was found in patients with CRC and the mouse model. A ligand-based high-throughput screening revealed a flavonoid abundant in soybeans, “genistein” (THIF: 4′,5,7-trihydroxyisoflavone), a new inhibitor of STAT1. A BODIPY-based genistein fluorescent probe was synthesized to study the mechanistic action of THIF and STAT1. THIF prevented the STAT1-STAT1 dimerization, abolished stemness and angiogenesis in CRC, and the in-vivo results in mice model attenuated tumor growth. In addition, genistein-based PROTAC (Proteolysis targeting chimera) degraders were synthesized to target STAT1 degradation in CRC. Abnormal glycosylation on the cell-surface is considered one of the hallmarks of cancer. Tracking down such glycosylation pathways can help to understand tumor progression, diagnosis and therapeutic development. As part of this work, we employed Metabolic oligosaccharide engineering (MOE) to modify glycans with an unnatural monosaccharide precursor containing a unique alkene tagged bioorthogonal chemical reporter group. The glycans are biosynthetically incorporated to the living cells and allowed to react with, a complementary bioorthogonal tetrazine functional group covalently linked to a set of BODIPY probes. Our designed BODIPY-based probes are fluorogenic with emission ranges from green to red-emitting BODIPY scaffold. Our present study indicates that these probes are specific fluorogenic labeling reagents for alkene-functionalized monosaccharides and is suitable for visualizing the localization of alkene-tagged glycosyl conjugates in cells by confocal microscopy. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-05-19T08:46:38Z No. of bitstreams: 0 | en |
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| dc.description.tableofcontents | Acknowledgment i
Abstract (Chinese) ii Abstract iv Abbreviations vi Table of Contents x List of Figures xiv List of Schemes xvi List of Tables xvi Chapter 1. Introduction to fluorescent imaging with particular emphasis on BODIPY i 1.1 Introduction 1 1.2 Fluorescence fundamentals 4 1.3 Brief history of fluorophores 5 1.4 Brief analysis of the rational design of fluorescent probes 7 1.5 Types of fluorescent probe Design 8 1.5.1 Photoinduced electron transfer (PeT): 9 1.5.2 FRET (Forster resonance energy transfer): 12 1.5.3 Fluorescence modulation through bond rotation: 14 1.6 Commonly used fluorophore scaffolds 15 1.7 BODIPY General Overview 18 1.8 BODIPY synthesis: 21 1.9 BODIPY structural modifications 23 1.9.1 BODIPY core modifications: 23 1.9.2 BODIPY alkylation: 24 1.9.3 BODIPY sulfonation and carbonyl-BODIPY: 24 1.9.4 Meso-amine BODIPY: 25 1.9.5 Meso-Propargyl-amine BODIPYs: 25 1.9.6 Nitro BODIPYs: 26 1.9.7 Cyano-BODIPY: 27 1.9.8 Halogenated BODIPYs: 27 1.9.9 Meso-aryl substituted BODIPYs: 30 1.10 BODIPY structural Properties: 31 1.10.1 BODIPY Photo stability: 31 1.10.2 BODIPY brightness: 31 1.10.3 BODIPY cytotoxicity 31 1.10.4 BODIPY cell permeability and targeted cell delivery: 32 1.11 Bioconjugation 34 1.11.1 Amine reactive groups: 34 1.11.2 Thiol reactive groups: 35 1.12 Future perspectives of BODIPY-based probes: 35 1.13 Conclusion of BODIPY-based fluorescent imaging 36 1.14 References 38 Chapter 2. Rational design and synthesis of BODIPY-based 1,2,4,5-tetrazine and 1,2,3-triazine fluorogenic probes for intracellular imaging 55 2.1 Introduction 55 2.2 Experimental Section of BODIPY-based tetrazine fluorogenic probes 57 2.2.1 Synthetic scheme, procedure and characterization of NIR-BODIPY-carboxylic acid 57 2.2.2 Synthetic scheme of the one-pot condition of BODIPY-carboxylic acids 62 2.2.3 Tetrazine conjugation with tert-butyl (2-aminoethyl)carbamate linker 64 2.2.4 Synthesis of NIR-BODIPY-tetrazine probe 65 2.2.5 Synthetic Procedures and Product Characterization of BODIPY-based 1,2,3-triazine fluorogenic probes 70 2.2.6 General synthetic procedure and product characterization of BODIPY-1,2,3-triazine conjugate 78 2.2.7 General synthetic procedure for AgNO3-mediated annulation of 1,2,3-triazine-BODIPY compounds 82 2.3 Results and Discussion 92 2.3.1 In vitro photophysical evaluation of the designed tetrazine probes 94 2.3.2 BODIPY-tetrazine probe monitoring of dienophile-modified glycans on the cell surface 94 2.3.3 BODIPY-based 1,2,3-triazine fluorogenic probes 101 2.3.5 Results of BODIPY-triazine probes: 102 2.4 Conclusion 104 2.5 References: 105 Chapter 3. Genistein-based BODIPY probe and PROTAC degraders targeting STAT1 to restrict cancer stem cells 107 3.1 Introduction 107 3.2 Experimental Section 109 3.2.1 Materials and Methods. 109 3.2.2 Synthesis of genistein-BODIPY conjugate 110 3.2.3 Synthesis of MOM-genistein 4`-esters: 115 3.2.4 Synthesis of MOM-genistein 4`–acid 119 3.2.5 Synthesis of E3-ligands 121 3.2.6 Synthesis of Linkers 123 3.2.7 Conjugation of E3-ligand with linkers 126 3.2.8 Genistein conjugation with E3 ligands via amide-coupling 128 3.2.9 Synthesis of final PROTAC products (MOM-deprotection) 136 3.3 Results and Discussion 143 3.3.1 STAT1 is upregulated in colorectal cancer 143 3.3.2 STAT1 KO reduces colorectal tumor growth in vivo 145 3.3.3 High‑throughput virtual screening of the SWEETLEAD database reveals that THIF exhibits anti‑STAT1 activity 145 3.3.4 THIF can bind to the STAT1 SH2 domain and block STAT1‑STAT1 dimerization 146 3.3.5 STAT1 enhances colorectal cancer stemness, while this effect is abolished by BODIPY‑THIF 148 3.3.6 STAT1 enhances angiogenesis in colorectal cancer, and BODIPY‑THIF shows antiangiogenic activity 150 3.3.7 BODIPY‑THIF reverses Δ9‑THC‑induced tumor growth in the mouse model of AOM/DSS‑induced colorectal cancer 150 3.4 Discussion 152 3.5 Conclusions 155 3.6 References 155 Chapter 4. A synthetic pregnenolone analog promotes microtubule dynamics and neural development 163 4.1 Introduction to steroids and their importance 163 4.2 Pregnenolone (P5) 164 4.2.1 Pregnenolone biosynthesis/steroidogenesis 165 4.2.2 Functions of Pregnenolone 167 4.2.3 Pregnenolone mechanism of action and its interaction with the target protein 171 4.2.4 Repercussions of pregnenolone deficiency in the CNS 175 4.2.5 The importance of pregnenolone fluorescent probes 177 4.3 Experimental Section 178 4.3.1 Materials and Methods. 178 4.3.2 Synthesis of Pregnenolone (P5) Derivatives at the C-3 position 179 4.3.3 Synthesis of P5-C3 position ester derivatives 186 4.3.4 Synthesis of P5-C3 position-acid derivatives 191 4.3.5 Synthesis of P5-C3 position-amide derivatives 193 4.3.6 Synthesis of P5-C7 position derivatives 198 4.3.7 Synthesis of BODIPY-based P5 fluorescent probe 201 4.3.8 Synthesis of NIR-BODIPY-based P5 fluorescent probe 205 4.4 Results 208 4.5 Discussion: 212 4.5.1 Stability of compound JJS-043: 215 4.5.2 Comparison of P5 and JJS-043 decay ratio via CuAAC click chemistry: 216 4.6 Conclusion 217 4.7 References 217 NMR spectra of all synthesized compounds 228 | - |
| dc.language.iso | en | - |
| dc.subject | MOE; | zh_TW |
| dc.subject | iEDDA | zh_TW |
| dc.subject | 四嗪; | zh_TW |
| dc.subject | P5; | zh_TW |
| dc.subject | 微管; | zh_TW |
| dc.subject | 神經軸突; | zh_TW |
| dc.subject | 金雀異黃酮; | zh_TW |
| dc.subject | STAT1; | zh_TW |
| dc.subject | BODIPY; | zh_TW |
| dc.subject | MOE; | en |
| dc.subject | BODIPY; | en |
| dc.subject | STAT1; | en |
| dc.subject | genistein; | en |
| dc.subject | neurite; | en |
| dc.subject | microtubules; | en |
| dc.subject | P5; | en |
| dc.subject | iEDDA | en |
| dc.subject | tetrazine; | en |
| dc.title | 基於 BODIPY 的螢光探針和生物偶聯物的設計和合成及其在生物系統上的應用 | zh_TW |
| dc.title | Design and Synthesis of BODIPY-Based Fluorescent Probes and Bioconjugates for Their Applications in Biological Systems | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 管永恕 | zh_TW |
| dc.contributor.coadvisor | Yung-Shu Kuan | en |
| dc.contributor.oralexamcommittee | 王宗盛;黃人則;李賢明;魏子堂 | zh_TW |
| dc.contributor.oralexamcommittee | Tsung-Shing Andrew Wang;Joseph Jen-Tse Huang;Hsien-Ming Lee;Tzu-Tang Thomas Wei | en |
| dc.subject.keyword | P5;,微管;,神經軸突;,金雀異黃酮;,STAT1;,BODIPY;,MOE;,四嗪;,iEDDA, | zh_TW |
| dc.subject.keyword | P5;,microtubules;,neurite;,genistein;,STAT1;,BODIPY;,MOE;,tetrazine;,iEDDA, | en |
| dc.relation.page | 350 | - |
| dc.identifier.doi | 10.6342/NTU202300701 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2023-03-30 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科學研究所 | - |
| dc.date.embargo-lift | 2028-03-28 | - |
| 顯示於系所單位： | 生化科學研究所 | |
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| ntu-111-2.pdf 此日期後於網路公開 2028-03-28 | 45 MB | Adobe PDF |
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