OPN-9652 is a potent and orally active covalent TEAD inhibitor, with a half-maximal inhibitory concentration (IC50) of 0.005 µM against TEAD in MSTO-211H cells, and it targets the central palmitate-binding pocket of TEAD. OPN-9652 can significantly reduce the activity of TEAD-dependent reporter genes and downregulate the expression levels of TEAD target genes (CTGF and CYR61). Notably, OPN-9652 can reverse the resistance of SOX10 knockout (SOX10 KO) resistant cells to the combination of BRAF inhibitor (BRAFi) and MAPK inhibitor (MAPKi), restoring their sensitivity to the drugs. In the xenograft mouse model of BRAF-mutant A375 cells, OPN-9652 can effectively delay the development of tumor drug resistance; specifically, this effect is manifested by a significant delay in the onset of tumor drug resistance after the combination of BRAFi and MEK inhibitor (MEKi) starting from the minimal residual disease (MRD) stage. At present, OPN-9652 can be used as a research tool for scientific research related to melanoma.

TEAD:5 nM