Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN)

Autor:	Zhongguo Wang, Goss Stryker Kauffman, Stephen Hubbs, Shawn Fessler, Lili Yao, Jennifer Castro, George P. Luke, Lu Wei, Mark T. Kershaw, Matthew W. Martin, Shawn Schiller, Crystal McKinnon, Angela V. Toms, Kenneth W. Bair, David S. Millan, David R. Lancia, Deepali Gotur, Li Hongbin
Rok vydání:	2019
Předmět:	Cellular activity High-throughput screening Clinical Biochemistry Drug Evaluation Preclinical Administration Oral Mice Nude Pharmaceutical Science 01 natural sciences Biochemistry Piperazines Mice Structure-Activity Relationship In vivo Cell Line Tumor Neoplasms Drug Discovery Animals Humans Transferase Binding site Molecular Biology Cell Proliferation Binding Sites biology 010405 organic chemistry Chemistry Organic Chemistry Protein Structure Tertiary Rats 0104 chemical sciences Malonyl Coenzyme A Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Fatty acid synthase Lipogenesis biology.protein Molecular Medicine Fatty Acid Synthases Half-Life
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 29:1001-1006
ISSN:	0960-894X
Popis:	The discovery, structure-activity relationships, and optimization of a novel class of fatty acid synthase (FASN) inhibitors is reported. High throughput screening identified a series of substituted piperazines with structural features that enable interactions with many of the potency-driving regions of the FASN KR domain binding site. Derived from this series was FT113, a compound with potent biochemical and cellular activity, which translated into excellent activity in in vivo models.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8e1607021e1e0b594aba77304e55e00 https://doi.org/10.1016/j.bmcl.2019.02.012 Zobrazit plný text záznamu Full Text from ScienceDirect