Triptolide

Triptolide

Identifiers
CAS Number	38748-32-2
3D model (JSmol)	Interactive image
ChEBI	CHEBI:9747
ChemSpider	97099
ECHA InfoCard	100.208.723
KEGG	C09204
PubChem CID	107985
InChI InChI=1S/C20H24O6/c1-8(2)18-13(25-18)14-20(26-14)17(3)5-4-9-10(7-23-15(9)21)11(17)6-12-19(20,24-12)16(18)22/h8,11-14,16,22H,4-7H2,1-3H3/t11-,12-,13-,14-,16+,17-,18-,19+,20+/m0/s1 Key: DFBIRQPKNDILPW-CIVMWXNOSA-N
SMILES CC(C)[C@@]12[C@@H](O1)[C@H]3[C@@]4(O3)[C@]5(CCC6=C([C@@H]5C[C@H]7[C@]4([C@@H]2O)O7)COC6=O)C
Properties
Chemical formula	C20H24O6
Molar mass	360.41 g·mol−1
Solubility in water	0.017 mg/mL
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Triptolide is a diterpenoid epoxide which is endogenously produced by 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. Due to its low solubility in water, several water-soluble analogs have been formulated, including Minnelide, which is currently in Phase I clinical trials.

Several putative target proteins of triptolide have been reported, including polycystin-2,ADAM10,DCTPP1,TAB1, and XPB. Multiple triptolide-resistant mutations exist in XPB (ERCC3) and its partner protein GTF2H4. 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. 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.

Minnelide is a more water-soluble analog of triptolide, and in-vivo (in the presence of phosphates) it is converted to triptolide. In a mouse model of pancreatic cancer it was "even more effective than gemcitabine". Phase 1 clinical trial planned for Dec 2012.

Glutriptolide 2, a glucose conjugate of triptolide with better solubility and lower toxicity, did not inhibit XPB activity in vitro, but exhibited remarkable tumor control in vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. And the preclinical research of Glutriptolide 2 was on the way by Rapafusyn Pharmaceuticals