5FI7

Crystal structure of human GAC in complex with inhibitor UPGL_00015: 2-phenyl-~{N}-[5-[(3~{S})-3-[[5-(2-phenylethanoylamino)-1,3,4-thiadiazol-2-yl]oxy]pyrrolidin-1-yl]-1,3,4-thiadiazol-2-yl]ethanamide

Summary for 5FI7

• Entry DOI: 10.2210/pdb5fi7/pdb
• Related: 5FI2 5FI6
• Descriptor: Glutaminase kidney isoform, mitochondrial, 2-phenyl-~{N}-[5-[(3~{S})-3-[[5-(2-phenylethanoylamino)-1,3,4-thiadiazol-2-yl]oxy]pyrrolidin-1-yl]-1,3,4-thiadiazol-2-yl]ethanamide (3 entities in total)
• Functional Keywords: glutaminase c, complex, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 238873.59

Authors

Huang, Q.,Cerione, R. (deposition date: 2015-12-22, release date: 2016-05-11, Last modification date: 2023-09-27)

Primary citation

McDermott, L.A.,Iyer, P.,Vernetti, L.,Rimer, S.,Sun, J.,Boby, M.,Yang, T.,Fioravanti, M.,O'Neill, J.,Wang, L.,Drakes, D.,Katt, W.,Huang, Q.,Cerione, R.
Design and evaluation of novel glutaminase inhibitors.
Bioorg.Med.Chem., 24:1819-1839, 2016

PubMed 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.

PubMed: 26988803
DOI: 10.1016/j.bmc.2016.03.009

Experimental method

X-RAY DIFFRACTION (2.5 Å)