Target Of Traditional Chinese Medicine Triptolide Found

The biological target of the natural product triptolide, a traditional Chinese medicine now in human clinical trials, has been identified. The work by Jun O. Liu of Johns Hopkins University School of Medicine and coworkers could aid the design of triptolide analogs (Nat. Chem. Biol., DOI: 10.1038/nchembio.522). Found in a plant called lei gong teng, or thunder god vine, triptolide is a diterpene with an unusual structure containing three adjacent epoxide groups. It has been used for centuries to treat myriad medical conditions; has been shown to have anti-inflammatory, immunosuppressive, contraceptive, and antitumor activities; and is currently in human clinical trials for cancer and other disorders. Despite its history, triptolide’s cellular target has been unknown. Liu and coworkers now show that it binds to XPB, a subunit of TFIIH, a transcription factor that helps initiate RNA polymerase-based transcription and helps repair DNA damage. The discovery “will facilitate the design of new inhibitors of XPB and other homologous DNA helicases as anticancer and antiproliferative drug leads,” the researchers say.