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

Summary for 5IXS

• Entry DOI: 10.2210/pdb5ixs/pdb
• Related: 5IXY
• Descriptor: L-lactate dehydrogenase A chain, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, 1,4,5,6-TETRAHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (7 entities in total)
• Functional Keywords: oxidoreductase tetramer, oxireductase-oxireductase inhibitor complex, oxireductase/oxireductase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P00338
• Total number of polymer chains: 4
• Total formula weight: 151900.63

Authors

Ultsch, M.,Eigenbrot, C. (deposition date: 2016-03-23, release date: 2016-09-14, Last modification date: 2023-09-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.05 Å)