Optimization of ether and aniline based inhibitors of lactate dehydrogenase.
Basic Information
ID: ALA4814030
Journal: Bioorg Med Chem Lett
Title: Optimization of ether and aniline based inhibitors of lactate dehydrogenase.
Authors: Christov PP, Kim K, Jana S, Romaine IM, Rai G, Mott BT, Allweil AA, Lamers A, Brimacombe KR, Urban DJ, Lee TD, Hu X, Lukacs CM, Davies DR, Jadhav A, Hall MD, Green N, Moore WJ, Stott GM, Flint AJ, Maloney DJ, Sulikowski GA, Waterson AG.
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.
CiteXplore: 33771585
DOI: 10.1016/j.bmcl.2021.127974
Patent ID: ┄