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

Basic Information

ID: ALA1154941

Journal: Bioorg Med Chem Lett

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

Authors: Bursavich MG, Parker DP, Willardsen JA, Gao ZH, Davis T, Ostanin K, Robinson R, Peterson A, Cimbora DM, Zhu JF, Richards B.

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.

CiteXplore: 20137940

DOI: 10.1016/j.bmcl.2010.01.058

Patent ID: ┄