9/4/2015 Triptolide ­ Wikipedia, the free encyclopedia

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Triptolide

IdentifiersCAS RegistryNumber

38748­32­2

PropertiesChemical formula C20H24O6

Molar mass 360.41 g·mol−1

Except where otherwise noted, data are given formaterials in their standard state (at 25 °C [77 °F],100 kPa).

Infobox references

TriptolideFrom Wikipedia, the free encyclopedia

Triptolide is a diterpenoid epoxide found in theThunder God Vine, Tripterygium wilfordii. It has invitro and in vivo activities against mouse models ofpolycystic kidney disease[1] and pancreatic cancer, butits physical properties limit its therapeutic potential.[2]Consequently, a synthetic prodrug, minnelide, is beingstudied clinically instead.[2]

Mechanism of action

Several putative target proteins of triptolide have beenreported, including polycystin­2,[3] ADAM10,[4]

DCTPP1,[5] TAB1,[6] and XPB.[7][8] Multipletriptolide­resistant mutations exist in XPB (ERCC3)and its partner protein GTF2H4.[9] However, notriptolide­resistant mutations were found inpolycystin­2, ADAM10, DCTPP1 and TAB1. Cys342of XPB was identified as the residue that undergoescovalent modification by the 12,13­epoxide group oftriptolide, and the XPB­C342T mutant rendered theT7115 cell line nearly completely resistant totriptolide.[7] The level of resistance conferred by the C342T mutation is about 100­fold higher than themost triptolide­resistant mutants previously identified.[9] Together, these results validate XPB as a targetresponsible for the antiproliferative activity of triptolide.

References1. Leuenroth, Stephanie (2007). "Triptolide is a traditional Chinese medicine­derived inhibitor of polycystic

kidney disease" (http://www.pnas.org/content/104/11/4389.abstract). PNAS 104 (11): 4389–4394.doi:10.1073/pnas.0700499104 (https://dx.doi.org/10.1073%2Fpnas.0700499104). Retrieved 18 October 2012.

2. Chugh, Rohit (2012). "A Preclinical Evaluation of Minnelide as a Therapeutic Agent Against PancreaticCancer" (http://stm.sciencemag.org/content/4/156/156ra139.abstract). Science Translational Medicine 4 (156):156ra139. doi:10.1126/scitranslmed.3004334 (https://dx.doi.org/10.1126%2Fscitranslmed.3004334).Retrieved 18 October 2012.

3. S. J. Leuenroth, D. Okuhara, J. D. Shotwell, G. S. Markowitz, Z. Yu, S. Somlo, C. M. Crews, Triptolide is atraditional Chinese medicine­derived inhibitor of polycystic kidney disease. Proc Natl Acad Sci U S A 2007,104, 4389­4394;

4. R. Soundararajan, R. Sayat, G. S. Robertson, P. A. Marignani,Triptolide: An inhibitor of a disintegrin andmetalloproteinase 10 (ADAM10) in cancer cells. Cancer Biol Ther 2009, 8, 2054­2062;

5. T. W. Corson, H. Cavga, N. Aberle, C. M. Crews, Triptolide directly inhibits dCTP pyrophosphatase.Chembiochem 2011, 12, 1767­1773;

6. Y. Lu, Y. Zhang, L. Li, X. Feng, S. Ding, W.Zheng, J. Li, P. Shen,TAB1: A Target of Triptolide inMacrophages. Chem. Biol. 2014, 21, 246 – 256.

7. Q. L. He, D. V. Titov, J. Li, M. Tan, Z. Ye, Y. Zhao, D. Romo, and J. O. Liu. Covalent Modification of aCysteine Residue in the XPB Subunit of the General Transcription Factor TFIIH Through Single EpoxideCleavage of the Transcription Inhibitor Triptolide. Angew. Chem. Int. Ed. 2015, 54, 1859 –1863

9/4/2015 Triptolide ­ Wikipedia, the free encyclopedia

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8. 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.

9. Y. Smurnyy, M. Cai, H. Wu, E. McWhinnie, J. A. Tallarico, Y.Yang, Y. Feng, DNA sequencing andCRISPR­Cas9 gene editing for target validation in mammalian cells. Nat. Chem. Biol. 2014, 10, 623 – 625

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Categories: Diterpenes Epoxides Lactones

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