Design and Evaluation of Novel Glutaminase Inhibitors

Autor:	Lee Apostle Mcdermott, Tianyi Yang, Richard A. Cerione, Lawrence Vernetti, William P. Katt, Jason W. O'Neill, Prema Iyer, Dylan J. Drakes, Michael Fioravanti, Melissa Boby, Jingran Sun, Qingqiu Huang, Shawn Rimer, Liwei Wang
Jazyk:	angličtina
Rok vydání:	2016
Předmět:	0301 basic medicine Gene isoform Models Molecular Clinical Biochemistry Heteroatom Benzeneacetamides Pharmaceutical Science Sulfides Biochemistry Article 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Glutaminase Cell Line Tumor Drug Discovery Thiadiazoles Moiety Humans Enzyme Inhibitors Molecular Biology Triple negative chemistry.chemical_classification Ligand efficiency Dose-Response Relationship Drug Molecular Structure Organic Chemistry 030104 developmental biology Enzyme chemistry 030220 oncology & carcinogenesis Drug Design Microsome Microsomes Liver Molecular Medicine
Popis:	A novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved C log Ps, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1deadb5112f65be8193275aa99f3b2b https://europepmc.org/articles/PMC6300166/ Zobrazit plný text záznamu