| Structural highlights
Disease
[LDHA_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]
Publication Abstract from PubMed
A 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.
References
- ↑ Maekawa M, Sudo K, Kanno T, Li SS. Molecular characterization of genetic mutation in human lactate dehydrogenase-A (M) deficiency. Biochem Biophys Res Commun. 1990 Apr 30;168(2):677-82. PMID:2334430
- ↑ 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. Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase. 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 doi:http://dx.doi.org/10.1016/j.bmcl.2014.10.067
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