Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90

Autor:	Geng Lifeng, James Marvin Veal, Jeffrey M. Partridge, Amy F. Barabasz, Steven E. Hall, James C. Otto, Barta Thomas E, Hanson Gunnar J, John W. Rice, Matthew Jenks, Wei Ma, Briana Foley, Patrick Fadden, Kenneth He Huang
Rok vydání:	2008
Předmět:	Models Molecular Stereochemistry Clinical Biochemistry Carbazoles Pharmaceutical Science Antineoplastic Agents Crystallography X-Ray Biochemistry Binding Competitive Small Molecule Libraries chemistry.chemical_compound Structure-Activity Relationship Adenosine Triphosphate Cell Line Tumor Drug Discovery polycyclic compounds Structure–activity relationship Humans HSP90 Heat-Shock Proteins Cytotoxicity Benzamide Molecular Biology Cell Proliferation biology Molecular Structure Organic Chemistry Stereoisomerism Hsp90 Small molecule Molecular Weight chemistry Chaperone (protein) biology.protein Molecular Medicine Signal transduction Drug Screening Assays Antitumor
Zdroj:	Bioorganicmedicinal chemistry letters. 18(12)
ISSN:	1464-3405
Popis:	Hsp90 maintains the conformational stability of multiple proteins implicated in oncogenesis and has emerged as a target for chemotherapy. We report here the discovery of a novel small molecule scaffold that inhibits Hsp90. X-ray data show that the scaffold binds competitively at the ATP site on Hsp90. Cellular proliferation and client assays demonstrate that members of the series are able to inhibit Hsp90 at nanomolar concentrations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f7c7cca52cc13617550beddfcf62d16 https://pubmed.ncbi.nlm.nih.gov/18511277 Zobrazit plný text záznamu Full Text from ScienceDirect