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Design and evaluation of novel glutaminase inhibitors.

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 ClogPs, 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.

SUBMITTER: McDermott LA

PROVIDER: S-EPMC6300166 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Design and evaluation of novel glutaminase inhibitors.

McDermott Lee A LA Iyer Prema P Vernetti Larry L Rimer Shawn S Sun Jingran J Boby Melissa M Yang Tianyi T Fioravanti Michael M O'Neill Jason J Wang Liwei L Drakes Dylan D Katt William W Huang Qingqiu Q Cerione Richard R

Bioorganic & medicinal chemistry 20160307 8

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 ClogPs, 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- ...[more]

PMID: 26988803

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