| Literature DB >> 33771585 |
Plamen P Christov1, Kwangho Kim1, Somnath Jana1, Ian M Romaine1, Ganesha Rai2, Bryan T Mott2, Alexander A Allweil1, Alexander Lamers1, Kyle R Brimacombe2, Daniel J Urban2, Tobie D Lee2, Xin Hu2, Christine M Lukacs3, Douglas R Davies3, Ajit Jadhav2, Matthew D Hall2, Neal Green3, William J Moore4, Gordon M Stott4, Andrew J Flint4, David J Maloney2, Gary A Sulikowski1, Alex G Waterson5.
Abstract
Lactate dehydrogenase (LDH) is a critical enzyme in the glycolytic metabolism pathway that is used by many tumor cells. Inhibitors of LDH may be expected to inhibit the metabolic processes in cancer cells and thus selectively delay or inhibit growth in transformed versus normal cells. We have previously disclosed a pyrazole-based series of potent LDH inhibitors with long residence times on the enzyme. Here, we report the elaboration of a new subseries of LDH inhibitors based on those leads. These new compounds potently inhibit both LDHA and LDHB enzymes, and inhibit lactate production in cancer cell lines.Entities:
Keywords: Cancer metabolism; LDH inhibitor; Medicinal chemistry; Structure activity relationships
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Year: 2021 PMID： 33771585 PMCID： PMC8113097 DOI： 10.1016/j.bmcl.2021.127974
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.940