Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2

Autor:	H. James Harwood, R. Kirk McPherson, Susan Tapley, Leanne M. Buzon, Kevin Daniel Freeman-Cook, Steven B. Coffey, Richard L. Elliott, Darcy Kohls, Liang Tong, Felix Vajdos, Meihua Tu, Eliot Sugarman, Shawn D. Doran, Francis Rajamohan, Eric S. Marr, Hailong Zhang, Wei Song, Kenneth J. DiRico, Jeffrey W. Corbett, Janet A. Houser, Sharad B. Murdande, William P. Esler, Martha L. Minich, Christopher J. Jones
Rok vydání:	2009
Předmět:	Models Molecular Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry Isozyme Small Molecule Libraries Structure-Activity Relationship Drug Discovery Transferase Animals Humans Enzyme Inhibitors Molecular Biology biology Drug discovery Chemistry Organic Chemistry Acetyl-CoA carboxylase Acetyl-CoA Carboxylase 1 Small molecule Pyruvate carboxylase Rats Isoenzymes Enzyme inhibitor biology.protein Molecular Medicine Acetyl-CoA Carboxylase
Zdroj:	Bioorganicmedicinal chemistry letters. 20(7)
ISSN:	1464-3405
Popis:	Screening Pfizer's compound library resulted in the identification of weak acetyl-CoA carboxylase inhibitors, from which were obtained rACC1 CT-domain co-crystal structures. Utilizing HTS hits and structure-based drug discovery, a more rigid inhibitor was designed and led to the discovery of sub-micromolar, spirochromanone non-specific ACC inhibitors. Low nanomolar, non-specific ACC-isozyme inhibitors that exhibited good rat pharmacokinetics were obtained from this chemotype.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c15f1a6bcbbc031e2169b1cbccc4dfb https://pubmed.ncbi.nlm.nih.gov/20219367 Zobrazit plný text záznamu Full Text from ScienceDirect