| 翻訳と辞書 |
Triptolide
Triptolide is a diterpenoid epoxide found in the Thunder God Vine, ''Tripterygium wilfordii''. It has ''in vitro'' and ''in vivo'' activities against mouse models of polycystic kidney disease and pancreatic cancer, but its physical properties limit its therapeutic potential. Consequently, a synthetic prodrug, minnelide, is being studied clinically instead.〔
==Mechanism of action==
Several putative target proteins of triptolide have been reported, including polycystin-2,〔S. J. Leuenroth, D. Okuhara, J. D. Shotwell, G. S. Markowitz, Z. Yu, S. Somlo, C. M. Crews, Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease. ''Proc Natl Acad Sci U S A'' 2007, 104, 4389-4394;〕 ADAM10,〔R. Soundararajan, R. Sayat, G. S. Robertson, P. A. Marignani,Triptolide: An inhibitor of a disintegrin and metalloproteinase 10 (ADAM10) in cancer cells. ''Cancer Biol Ther'' 2009, 8, 2054-2062;〕 DCTPP1,〔T. W. Corson, H. Cavga, N. Aberle, C. M. Crews, Triptolide directly inhibits dCTP pyrophosphatase. ''Chembiochem'' 2011, 12, 1767-1773;〕 TAB1,〔Y. Lu, Y. Zhang, L. Li, X. Feng, S. Ding, W.Zheng, J. Li, P. Shen,TAB1: A Target of Triptolide in Macrophages. ''Chem. Biol.'' 2014, 21, 246 – 256.〕 and XPB.〔〔D. V. Titov, B. Gilman, Q. L.He, S. Bhat,W. K. Low, Y. Dang,M.Smeaton, A. L. Demain, P. S. Miller, J. F. Kugel, J. A. Goodrich,J. O. Liu, XPB, a subunit of TFIIH, is a target of the natural product triptolide. ''Nat. Chem. Biol.'' 2011, 7, 182 – 188.〕 Multiple triptolide-resistant mutations exist in XPB (ERCC3) and its partner protein GTF2H4.〔Y. Smurnyy, M. Cai, H. Wu, E. McWhinnie, J. A. Tallarico, Y.Yang, Y. Feng, DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells. ''Nat. Chem. Biol''. 2014, 10, 623 – 625〕 However, no triptolide-resistant mutations were found in polycystin-2, ADAM10, DCTPP1 and TAB1. Cys342 of XPB was identified as the residue that undergoes covalent modification by the 12,13-epoxide group of triptolide, and the XPB-C342T mutant rendered the T7115 cell line nearly completely resistant to triptolide.〔Q. L. He, D. V. Titov, J. Li, M. Tan, Z. Ye, Y. Zhao, D. Romo, and J. O. Liu. Covalent Modification of a Cysteine Residue in the XPB Subunit of the General Transcription Factor TFIIH Through Single Epoxide Cleavage of the Transcription Inhibitor Triptolide. ''Angew. Chem. Int. Ed.'' 2015, 54, 1859 –1863〕 The level of resistance conferred by the C342T mutation is about 100-fold higher than the most triptolide-resistant mutants previously identified.〔 Together, these results validate XPB as a target responsible for the antiproliferative activity of triptolide.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
■ウィキペディアで「Triptolide」の詳細全文を読む
スポンサード リンク
| 翻訳と辞書 : 翻訳のためのインターネットリソース |
Copyright(C) kotoba.ne.jp 1997-2016. All Rights Reserved.
|
|