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

Matthew G. Bursavich; 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

doi:10.1016/j.bmcl.2010.01.058

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

Matthew G. Bursavich, 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

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1677-1679
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2010.01.058
State	Published - Mar 1 2010

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2010.01.058

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title = "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.",

author = "Bursavich, {Matthew G.} and Parker, {Daniel P.} and Willardsen, {J. Adam} and Gao, {Zhong Hua} and Thaylon Davis and Kirill Ostanin and Rosann Robinson and Ashley Peterson and Cimbora, {Daniel M.} and Zhu, {Ju Fen} and Burt Richards",

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doi = "10.1016/j.bmcl.2010.01.058",

language = "English (US)",

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AU - Bursavich, Matthew G.

AU - Parker, Daniel P.

AU - Willardsen, J. Adam

AU - Gao, Zhong Hua

AU - Davis, Thaylon

AU - Ostanin, Kirill

AU - Robinson, Rosann

AU - Peterson, Ashley

AU - Cimbora, Daniel M.

AU - Zhu, Ju Fen

AU - Richards, Burt

PY - 2010/3/1

Y1 - 2010/3/1

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AB - 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.

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JO - Bioorganic and Medicinal Chemistry Letters

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ER -

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

Abstract

All Science Journal Classification (ASJC) codes

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