Design and evaluation of novel glutaminase inhibitors. Issue 8 (15th April 2016)

• Record Type: Journal Article
• Authors: McDermott, Lee A.; Iyer, Prema; Vernetti, Larry; Rimer, Shawn; Sun, Jingran; Boby, Melissa; Yang, Tianyi; Fioravanti, Michael; O'Neill, Jason; Wang, Liwei; Drakes, Dylan; Katt, William; Huang, Qingqiu; Cerione, Richard
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 8(2016)
• Page Start: 1819
• Page End: 1839
• Publication Date: 2016-04-15
• Subjects: GAC -- Novel glutaminase inhibitors -- BPTES -- CB-839; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.03.009
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 P s, 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.