 | |
| Names | |
|---|---|
| Preferred IUPAC name (3bS,4aS,5aS,6R,6aR,7aS,7bS,8aS,9bS)-6-Hydroxy-8b-methyl-6a-(propan-2-yl)-3b,4,4a,5a,6,6a,7a,7b,8a,8b,9,10-dodecahydrotris(oxireno)[2′,3′:4b,5;2′′,3′′:6,7;2′′′,3′′′:8a,9]phenanthro[1,2-c]furan-1(3H)-one | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.208.723 |
| KEGG | |
| UNII | |
| |
| |
| Properties | |
| C20H24O6 | |
| Molar mass | 360.406 g·mol−1 |
| 0.017 mg/mL[1] | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Triptolide is aditerpenoidepoxide which is produced by the thunder god vine,Tripterygium wilfordii. It hasin vitro andin vivo activities againstmouse models ofpolycystic kidney disease[2] andpancreatic cancer, but itsphysical properties[3] and severe toxicity[4] limit its therapeutic potential. Consequently, a synthetic water-solubleprodrug, minnelide, is being studiedclinically instead.[3][5]
Triptolide is a component ofContraPest, acontraceptivepest control liquid used to reduce rat populations in the United States.
Several putative target proteins of triptolide have been reported, includingpolycystin-2,[6]ADAM10,[7]DCTPP1,[8]TAB1,[9] andXPB.[10][11] Multiple triptolide-resistant mutations exist in XPB (ERCC3) and its partner proteinGTF2H4.[12] 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.[10] The level of resistance conferred by the C342T mutation is about 100-fold higher than the most triptolide-resistant mutants previously identified.[12] Together, these results validate XPB as a target responsible for the antiproliferative activity of triptolide. The disruption ofsuper-enhancernetworks has also been suggested as a mechanism of action.[13]
Minnelide is a more water-soluble syntheticprodrug of triptolide which is converted to triptolidein vivo.[3][14] In a preclinical mouse model of pancreatic cancer, it was "even more effective thangemcitabine". ItsPhase II clinical trials are expected to conclude in February 2019.[15]
Glutriptolide, a glucose conjugate of triptolide with better solubility and lower toxicity, did not inhibit XPB activityin vitro, but exhibited tumor controlin vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells.[16] A second generation glutriptolide has been recently reported for targeting hypoxic cancer cells with increased glucose transporter expression.[17]
 | You can helpexpand this article with text translated fromthe corresponding article in German. (October 2012)Click [show] for important translation instructions.
|
