Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, United States.
National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
Bioorg Med Chem Lett. 2021 Jun 1;41:127974. doi: 10.1016/j.bmcl.2021.127974. Epub 2021 Mar 24.
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.
乳酸脱氢酶（LDH）是糖酵解代谢途径中的关键酶，许多肿瘤细胞都在使用。LDH 的抑制剂有望抑制癌细胞的代谢过程，从而选择性地延迟或抑制转化细胞与正常细胞的生长。我们之前已经披露了一系列基于吡唑的强效 LDH 抑制剂，这些抑制剂在酶上的停留时间很长。在这里，我们报告了基于这些先导化合物的新的 LDH 抑制剂亚系列的阐述。这些新化合物强烈抑制 LDHA 和 LDHB 两种酶，并抑制癌细胞系中的乳酸生成。
