Development of a novel lactate dehydrogenase A inhibitor with potent antitumor activity and immune activation

• DOI: 10.1111/cas.15468
• Publication Date: 2022-06-20T09:55:42Z
• Authors: Mengyan Du; Ting Yu; Qinjinge Zhan; Han Li; Yiping Zou; Meiyu Geng; Tao Meng; Zuoquan Xie
• Keywords: Lactate dehydrogenase A

Lactate accumulation in the tumor microenvironment was shown to be closely related growth and immune escape, suppression of lactate production by inhibiting dehydrogenase A (LDHA) has been pursued as a potential novel antitumor strategy. However, only few potent LDHA inhibitors have developed most them did not show effects vivo. To this end, we designed new obtained inhibitor, ML-05. ML-05 inhibited cellular cell proliferation, which associated with inhibition ATP induction reactive oxygen species G1 phase arrest. In mouse B16F10 melanoma model, intratumoral injection significantly reduced production, growth, released response T subsets (Th1 GMZB+ CD8 cells) microenvironment. Moreover, treatment combined programmed death-1 Ab or stimulator interferon genes protein (STING) could sensitize activity model. Collectively, ML-05, that elicited profound when injected locally, activation immunity. addition, immunotherapies, suggests great translational value.