2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)

  • Bioorg Med Chem Lett. 2010 Mar 1;20(5):1677-9. doi: 10.1016/j.bmcl.2010.01.058.
Matthew G Bursavich  1 ,  Daniel P Parker ,  J Adam Willardsen ,  Zhong-Hua Gao ,  Thaylon Davis ,  Kirill Ostanin ,  Rosann Robinson ,  Ashley Peterson ,  Daniel M Cimbora ,  Ju-Fen Zhu ,  Burt Richards
Affiliations
  • 1. Medicinal Chemistry, Myriad Pharmaceuticals, Inc., 305 South Chipeta Way, Salt Lake City, UT 84108, United States. [email protected]
PMID: 20137940 DOI: 10.1016/j.bmcl.2010.01.058
Abstract

Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase family with a central role in the ubiquitin-degradation of misfolded proteins. VCP also exhibits antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1,3-thiazoles are potent drug-like inhibitors of this enzyme. The identified compounds show low nanomolar VCP potency, demonstrate SAR trends, and show activity in a mechanism based cellular assay. This series of compounds represents the first steps towards a novel, small molecule VCP inhibitor as a Cancer therapeutic.