請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17939
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 符文美 | |
dc.contributor.author | Ting-Hao Kuo | en |
dc.contributor.author | 郭廷濠 | zh_TW |
dc.date.accessioned | 2021-06-08T00:46:38Z | - |
dc.date.copyright | 2015-09-24 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-07-28 | |
dc.identifier.citation | Almeida M, Iyer S, Martin-Millan M, Bartell SM, Han L, Ambrogini E, Onal M, Xiong J, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. Estrogen receptor-α signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Invest. 2013. 123(1): 394–404.
Ankita Modi, Shiva Sajjan, Sampada Gandhi. Challenges in implementing and maintaining osteoporosis therapy. Int J Womens Health. 2014. 6: 759–769 An, H.; Kim, N.-J.; Jung, J.-W.; Jang, H.; Park, J.-W.; Suh, Y.-G. Design, synthesis and insight into the structure−activity relationship of 1,3-disubstituted indazoles as novel HIF-1 inhibitors. Bioorg. Med. Chem. Lett. 2011. 21: (21) 6297−6300. Barbara Janson Cohen, Jason Taylor. Memmler's Structure And Function Of The Human Body, Ninth Edition. 2009. Brendan F Boyce and Lianping Xing. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007. 9: S1. Bo Abrahamsen, Clive Osmond and Cyrus Cooper. Life Expectancy in Patients Treated for Osteoporosis: Observational Cohort Study Using National Danish Prescription Data. J Bone Miner Res. 2015. 2478 Chou, L. C.; Huang, L. J.; Hsu, M. H.; Fang, M. C.; Yang, J. S.; Zhuang, S. H.; Lin, H. Y.; Lee, F. Y.; Teng, C. M.; Kuo, S. C. Synthesis of 1-benzyl-3-(5-hydroxymethyl-2-furyl)selenolo[3,2-c]pyrazole derivatives as new anticancer agents. Eur. J. Med. Chem. 2010. 45: 1395−1402. Collot, V.; Dallemagne, P.; Bovy, P. R.; Rault, S. Suzuki-type cross-coupling reaction of 3-iodoindazoles with aryl boronic acids: A general and flexible route to 3-arylindazoles. Tetrahedron. 1999. 55: 6917−6922. Charles R. Craig, Robert E. Stitzel. Modern Pharmacology With Clinical Applications, Sixth Edition. 2003. Daniel D. Chiras. Human Biology 8th edition. Jones & Bartlett Learning. 2013. Dawson-Hughes, B.; Looker, A. C.; Tosteson, A. N.; Johansson, H.; Kanis, J. A.; Melton, L. J., 3rd, The potential impact of the National Osteoporosis Foundation guidance on treatment eligibility in the USA: an update in NHANES 2005-2008. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA . 2012, 23 (3), 811-20 Deborah Veis Novack. Role of NF-κB in the skeleton. Cell Res. 2011. 21(1): 169–182 Deborah Veis Novack, Li Yin, Amanda Hagen-Stapleton, Robert D. Schreiber, David V. Goeddel, F. Patrick Ross, and Steven L. Teitelbaum1.The IκB Function of NF-κB2 p100 Controls Stimulated Osteoclastogenesis. J Exp Med. 2003. 198(5): 771–781. Derek G. Waller, Andrew G. Renwick, Keith Hillier. Medical Pharmacology and Therapeutics. Saunders. 2009. Elaine N. Marieb, Jon B. Mallatt & Patricia Brady Wilhelm. Human Anatomy, 5/E. Pearson. 2008. Elaine Mary Aldred. Pharmacology: A Handbook for Complementary Healthcare Professionals, 1e. Churchill Livingstone. 2008. Elazar Zelzer, Bjorn R. Olsen.The genetic basis for skeletal diseases. Nature. 2003. 423, 343-348. Eleni Maniati, Maud Bossard, Natalie Cook et al.Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. J Clin Invest. 2011. 121(12):4685–4699. Gentry Steele. D, Claud A. Bramblett. The Anatomy and Biology of the Human Skeleton. Texas A&M University Consortium Press. 1988. Gilmore T D. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene . 2006. 25, 6680–6684. Humphrey P. Rang, James M. Ritter, Rod J. Flower. Rang and Dale's Pharmacology, 6e.Churchill Livingstone. 2007. Jahangir Moini. Focus on Pharmacology (1st Edition). Prentice Hall. 2008. Jerome carolino, M.D., Juan A. Perez, M.D., and Anca Popa, M.D., Saint Mary Hospital, Hoboken, New Jersey. Osteopetrosis. Am Fam Physician. 1998. 57(6):1293-1296. John P. Bilezikian, Lawrence G. Raisz, T. John Martin. Principles of Bone Biology Third Edition. 2008 Kevin T. Patton, PhD and Gary A. Thibodeau. Anthony's Textbook of Anatomy & Physiology 19th edition. 2010. Kim KJ, Yeon JT, Choi SW, Moon SH, Ryu BJ, Yu R, Park SJ, Kim SH, Son YJ. Decursin inhibits osteoclastogenesis by downregulating NFATc1 and blocking fusion of pre-osteoclasts. Bone. 2015. pii: S8756-3282(15)00297-5. Kohli, S. S.; Kohli, V. S., Role of RANKL-RANK/osteoprotegerin molecular complex in bone remodeling and its immunopathologic implications. Indian J Endocrinol Metab. 2011. 15 (3), 175-81 Lawrence G. Raisz. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005. 115(12): 33 Lee Na Kyung. Molecular Understanding of Osteoclast Differentiation and Physiology. Endocrinol Metab. 2010. 5(4):264-269. Lee, F. Y.; Lien, J. C.; Huang, L. J.; Huang, T. M.; Tsai, S. C.; Teng, C. M.; Wu, C. C.; Cheng, F. C.; Kuo, S. C. Synthesis of 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole analogues as novel anti-platelet agents. J. Med. Chem. 2001. 44, 3746−3749. Lien, J. C.; Lee, F. Y.; Huang, L. J.; Pan, S. L.; Guh, J. H.; Teng, C. M.; Kuo, S. C. 1-Benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole (YC-1) derivatives as novel inhibitors against sodium nitroprusside-induced apoptosis. J. Med. Chem. 2002. 45, 4947−4949. Li X, Wei W, Huynh H, Zuo H, Wang X, Wan Y.Nur77 prevents excessive osteoclastogenesis by inducing ubiquitin ligase Cbl-b to mediate NFATc1 self-limitation. Elife. 2015. 14;4. Maeda, S. S.; Lazaretti-Castro, M., An overview on the treatment of postmenopausal osteoporosis. Arq Bras Endocrinol Metabol. 2014. 58 (2), 162-71. Menéndez-Gutiérrez MP, Rőszer T, Fuentes L, Núñez V, Escolano A, Redondo JM, De Clerck N, Metzger D, Valledor AF, Ricote M. Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling .J Clin Invest. 2015. 125(2):809-23. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. 2014. Version 1 Nelson B. Watts, Pauline M. Camacho, Steven T. Harris, Michael Kleerekoper, Michael R. McClung, Rachel Pessah Pollack. AACE Postmenopausal Osteoporosis Guidelines. 2010. Robin Arnold, Ken Ashwell, Deborah Bryce, Carol Fallows, Martin Fallows, John Frith, John Gallo, Brain Gaynor, Rakesh Kumar, Peter Lavelle, Lesley Lopes, Karen McGhee, Michael Roberts, Elizabeth Tancred, Dzung Vu, Phil Waite. Anatomica's Body Atlas. 2002. Roman-Garcia, P.; Quiros-Gonzalez, I.; Mottram, L.; Lieben, L.; Sharan, K.; Wangwiwatsin, A.; Tubio, J.; Lewis, K.; Wilkinson, D.; Santhanam, B.; Sarper, N.; Clare, S.; Vassiliou, G. S.; Velagapudi, V. R.; Dougan, G.; Yadav, V. K., Vitamin B12-dependent taurine synthesis regulates growth and bone mass. J Clin Invest. 2014. 124 (7), 2988-3002 Ross, F. P., M-CSF, c-Fms, and signaling in osteoclasts and their precursors. Ann N Y Acad Sci. 2006. 1068, 110-6. Sergio Vaira, Trevor Johnson, Angela C. Hirbe, Muhammad Alhawagri, Imani Anwisye, Benedicte Sammut, Julie O'Neal, Wei Zou, Katherine N. Weilbaecher, Roberta Faccio, and Deborah Veis Novack.RelB is the NF-κB subunit downstream of NIK responsible for osteoclast differentiation. Proc Natl Acad Sci U S A. 2008. 105(10):3897-902. Teixeira MZ. Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude. Homeopathy. 2012.101(4):231-42. Wang, H.; Liu, J.; Yin, Y.; Wu, J.; Wang, Z.; Miao, D.; Sun, W. Recombinant human parathyroid hormone related protein 1−34 and 1−84 and their roles in osteoporosis treatment. PLoS One. 2014. 9 (2): e88237. Wendy Green. Denosumab (Prolia) Injection, A New Approach to the Treatment of Women With Postmenopausal Osteoporosis. P T. 2010. 35(10): 553–559. Wu K, Lin TH, Liou HC, Lu DH, Chen YR, Fu WM, Yang RS.Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation. Osteoporos Int. 2013. 24(8):2201-14. Yan Xiu, Hao Xu, Chen Zhao et al.Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation. J Clin Invest. 2014. 124(1): 297-310. Yavropoulou, M. P.; Yovos, J. G., Osteoclastogenesis--current knowledge and future perspectives. J Musculoskelet Neuronal Interact. 2008. 8 (3): 204-16 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17939 | - |
dc.description.abstract | 隨著人類壽命的延長,老化相關之疾病的發生將更加普遍,如 : 骨質疏鬆症。目前骨質疏鬆症相關治療藥物仍有無法承受的副作用,以及療效不佳的問題,在現今的治療中,我們仍需要有效的新穎治療藥物,因此,我們設計合成出一系列之吡唑衍生物,更進一步測試這些衍生物在骨質疏鬆症相關活體外與活體內實驗之效力。最佳的衍生物為化合物13,其具有二甲氨基乙基之結構,化合物13能有效抑制活體外破骨細胞生成與蝕骨活性,化合物13對於蝕骨細胞生成之前期的抑制功效優於後期。在骨質疏鬆動物模式卵巢切除母鼠中,可以發現化合物13可以有效地抑制總骨小樑體積、骨小樑數量及骨小樑厚度的降低,另一方面,化合物13也可以拮抗卵巢切除母鼠血清中的蝕骨指標與造骨指標的上升。綜上,化合物13具有發展為治療骨質疏鬆症之新穎藥物之潛力。 | zh_TW |
dc.description.abstract | As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2- (dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclast’s early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T00:46:38Z (GMT). No. of bitstreams: 1 ntu-104-R02443001-1.pdf: 2765589 bytes, checksum: e5c7768cb2ccd885f76d5403f75ad55f (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | Abbreviations III
摘要 V Abstract VI Chapter 1 Introduction 1 1-1 Types of bones 1 1-2 Osteoporosis and bone metabolism 3 1-3 Relationship between RANKL-RANK interaction and NF-κB pathway 8 1-4 Therapeutic agents for osteoporosis 11 Chapter 2 Materials and Methods 13 Chapter 3 Results 25 3-1 Chemistry 25 3-2 Inhibition of osteoclastogenesis by pyrazole derivatives 27 3-3 Inhibition of osteoclastogenesis and bone resorption activity of osteoclast by compound 13 28 3-4 Compound 13 inhibits RANKL-induced NF-κB activation 30 3-5 Compound 13 inhibits osteoporosis in ovariectomized OVX mice 31 3-6 Compound 13 antagonizes OVX-induced change of serum bone resorption and bone formation markers 32 Chapter 4 Discussion 33 Reference 49 | |
dc.language.iso | en | |
dc.title | 新穎吡唑衍生物應用於治療骨質疏鬆之潛力 | zh_TW |
dc.title | Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 楊榮森,林琬琬,劉宏輝,楊春茂 | |
dc.subject.keyword | 骨質疏鬆症,?唑衍生物,化合物13,破骨細胞,蝕骨, | zh_TW |
dc.subject.keyword | osteoporosis,pyrazole derivatives,compound 13,osteoclast,bone resorption, | en |
dc.relation.page | 53 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2015-07-28 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-104-1.pdf 目前未授權公開取用 | 2.7 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。