4rls
From Proteopedia
Lactate Dehydrogenase in complex with inhibitor compound 47
Structural highlights
DiseaseLDHA_HUMAN Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:612933. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.[1] FunctionPublication Abstract from PubMedA series of 3,6-disubstituted dihydropyrones were identified as inhibitors of human lactate dehydrogenase (LDH)-A. Structure activity relationships were explored and a series of 6,6-spiro analogs led to improvements in LDHA potency (IC50 <350nM). An X-ray crystal structure of an improved compound bound to human LDHA was obtained and it illustrated additional opportunities to enhance the potency of these compounds, resulting in the identification of 51 (IC50=30nM). Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase.,Fauber BP, Dragovich PS, Chen J, Corson LB, Ding CZ, Eigenbrot C, Labadie S, Malek S, Peterson D, Purkey HE, Robarge K, Sideris S, Ultsch M, Wei B, Yen I, Yue Q, Zhou A Bioorg Med Chem Lett. 2014 Dec 15;24(24):5683-7. doi: 10.1016/j.bmcl.2014.10.067., Epub 2014 Oct 27. PMID:25467161[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
