TBOPP

TBOPP is a selective small molecule inhibitor of Dedicator of cytokinesis 1 (DOCK1), a guanine nucleotide exchange factor (GEF) that activates the Rho GTPase RAC1. In hepatocellular carcinoma (HCC), DOCK1 has been identified as a key mediator of resistance to metformin; metformin treatment can induce DOCK1 phosphorylation, which in turn activates RAC1 to promote tumor cell survival. TBOPP works by inhibiting DOCK1, thereby preventing RAC1 activation and sensitizing HCC cells to the anti-tumor effects of metformin. Preclinical studies in liver cancer cell lines, patient-derived organoids, and xenograft mouse models have demonstrated that TBOPP potentiates metformin's activity, suggesting a potential synthetic lethal therapeutic strategy for HCC patients with high DOCK1 expression levels.

Other names

1-(2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)ethyl)pyrrolidine-2,5-dione