Corson, Timothy W.Cavga, HüseyinAberle, NicholasCrews, Craig M2013-08-202013-08-202011-07Corson, T. W., Cavga, H., Aberle, N., & Crews, C. M. (2011). Triptolide directly inhibits dCTP pyrophosphatase. ChemBioChem, 12(11), 1767-1773.https://hdl.handle.net/1805/3437Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti-inflammatory, antifertility, and antipolycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide-interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide.en-USDCTPP1natural productsnucleotidesphotoaffinity labelingtriptolideArticle