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

Matthew G. Bursavich, Daniel P. Parker, J. Adam Willardsen, Zhonghua Gao, Thaylon Davis, Kirill Ostanin, Rosann Robinson, Ashley Peterson, Daniel M. Cimbora, Ju Fen Zhu, Burt Richards

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1677-1679
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number5
DOIs
StatePublished - Mar 1 2010

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Thiazoles
NF-kappa B
Enzyme Inhibitors
Ubiquitin
Proteolysis
Adenosine Triphosphatases
Assays
Chemical activation
Neoplasm Metastasis
Degradation
Molecules
Pharmaceutical Preparations
Neoplasms
Proteins
Therapeutics
CDC48 protein

All Science Journal Classification (ASJC) codes

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

Cite this

Bursavich, M. G., Parker, D. P., Willardsen, J. A., Gao, Z., Davis, T., Ostanin, K., ... Richards, B. (2010). 2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97). Bioorganic and Medicinal Chemistry Letters, 20(5), 1677-1679. https://doi.org/10.1016/j.bmcl.2010.01.058
Bursavich, Matthew G. ; Parker, Daniel P. ; Willardsen, J. Adam ; Gao, Zhonghua ; Davis, Thaylon ; Ostanin, Kirill ; Robinson, Rosann ; Peterson, Ashley ; Cimbora, Daniel M. ; Zhu, Ju Fen ; Richards, Burt. / 2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97). In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 5. pp. 1677-1679.
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Bursavich, MG, Parker, DP, Willardsen, JA, Gao, Z, Davis, T, Ostanin, K, Robinson, R, Peterson, A, Cimbora, DM, Zhu, JF & Richards, B 2010, '2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 5, pp. 1677-1679. https://doi.org/10.1016/j.bmcl.2010.01.058

2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97). / Bursavich, Matthew G.; Parker, Daniel P.; Willardsen, J. Adam; Gao, Zhonghua; Davis, Thaylon; Ostanin, Kirill; Robinson, Rosann; Peterson, Ashley; Cimbora, Daniel M.; Zhu, Ju Fen; Richards, Burt.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 5, 01.03.2010, p. 1677-1679.

Research output: Contribution to journalArticle

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AU - Bursavich, Matthew G.

AU - Parker, Daniel P.

AU - Willardsen, J. Adam

AU - Gao, Zhonghua

AU - Davis, Thaylon

AU - Ostanin, Kirill

AU - Robinson, Rosann

AU - Peterson, Ashley

AU - Cimbora, Daniel M.

AU - Zhu, Ju Fen

AU - Richards, Burt

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