5IXS

Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 9: (6R)-3-[(2-chlorophenyl)sulfanyl]-4-hydroxy-6-(3-hydroxyphenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one

5IXS の概要

• エントリーDOI: 10.2210/pdb5ixs/pdb
• 関連するPDBエントリー: 5IXY
• 分子名称: L-lactate dehydrogenase A chain, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, 1,4,5,6-TETRAHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (7 entities in total)
• 機能のキーワード: oxidoreductase tetramer, oxireductase-oxireductase inhibitor complex, oxireductase/oxireductase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P00338
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 151900.63

構造登録者

Ultsch, M.,Eigenbrot, C. (登録日: 2016-03-23, 公開日: 2016-09-14, 最終更新日: 2023-09-27)

主引用文献

Purkey, H.E.,Robarge, K.,Chen, J.,Chen, Z.,Corson, L.B.,Ding, C.Z.,DiPasquale, A.G.,Dragovich, P.S.,Eigenbrot, C.,Evangelista, M.,Fauber, B.P.,Gao, Z.,Ge, H.,Hitz, A.,Ho, Q.,Labadie, S.S.,Lai, K.W.,Liu, W.,Liu, Y.,Li, C.,Ma, S.,Malek, S.,O'Brien, T.,Pang, J.,Peterson, D.,Salphati, L.,Sideris, S.,Ultsch, M.,Wei, B.,Yen, I.,Yue, Q.,Zhang, H.,Zhou, A.
Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice.
Acs Med.Chem.Lett., 7:896-901, 2016

PubMed Abstract: A series of trisubstituted hydroxylactams was identified as potent enzymatic and cellular inhibitors of human lactate dehydrogenase A. Utilizing structure-based design and physical property optimization, multiple inhibitors were discovered with <10 μM lactate IC in a MiaPaca2 cell line. Optimization of the series led to , a potent cell active molecule (MiaPaca2 IC = 0.67 μM) that also possessed good exposure when dosed orally to mice.

PubMed: 27774125
DOI: 10.1021/acsmedchemlett.6b00190

実験手法

X-RAY DIFFRACTION (2.05 Å)