Application of 1,2,3,6-tetra-o-galloyl-Β-d-glucose and derivatives thereof as an antitumor drug and / or a tumor-sensitizing drug

Abstract

The present invention belongs to the technical field of biomedicine, and specifically relates to the application of 1,2,3,6-tetra-O-galloyl-β-D-glucose and derivatives thereof as an antitumor drug and / or a tumor sensitizing drug. The present invention, for the first time, reveals that AARS1, as a lactylation-modifying enzyme, is capable of catalyzing the lactylation modification of NMNAT1, thereby enhancing its interaction with PARP1, promoting the activity of PARP1, and resulting in resistance of tumor cells with homologous recombination repair deficiency to PARP inhibitors. Based on this novel mechanism, the present invention screens and verifies that the small-molecule compound 1,2,3,6-tetra-O-galloyl-β-D-glucose can effectively inhibit the catalytic activity of AARS1, reduce the lactylation modification level of NMNAT1, and thereby restore the sensitivity of drug- resistant tumors to PARP inhibitors. FIG.6