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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

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

doi

10.1016/j.bmcl.2010.01.058

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

1677-9

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)00070-3

journal_volume

20

pub_type

杂志文章

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