5FI2

Crystal structure of human GAC in complex with inhibitor UPGL_00009: 2-phenyl-~{N}-[5-[[(3~{R})-1-[5-(2-phenylethanoylamino)-1,3,4-thiadiazol- 2-yl]pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]ethanamide

5FI2 の概要

• エントリーDOI: 10.2210/pdb5fi2/pdb
• 関連するPDBエントリー: 5D3O 5FI6 5FI7
• 分子名称: Glutaminase kidney isoform, mitochondrial, 2-phenyl-~{N}-[5-[[(3~{R})-1-[5-(2-phenylethanoylamino)-1,3,4-thiadiazol-2-yl]pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]ethanamide (3 entities in total)
• 機能のキーワード: glutaminase c, complex, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 238871.62

構造登録者

Huang, Q.,Cerione, R. (登録日: 2015-12-22, 公開日: 2016-05-11, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)