CtBP1/BARS inhibitor Comp.11 is a potent, selective inhibitor targeting the C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS), directly binds and inhibits the CtBP1/BARS protein-partners interaction with Kd of 0.66 uM.
Comp.11 affects the oligomerization of CtBP1/BARS and inhibits the binding of CtBP1/BARS to partners involved in both transcription and membrane fission.
Comp.11 impairs the CtBP1/BARS-controlled protein transport and cell entry into mitosis.
Comp.11 inhibits cell proliferation by inducing G0/G1 phase cell cycle arrest in melanoma cells with EC50 of 23.71 μM on A375MM and of 19.36 μM on B16F10 cells (24 h).
Comp.11 induces apoptosis in melanoma cells, impairs motility and invasion of melanoma cells by affecting the CtBP1/BARS- mediated transcription of EMT-related genes.
Comp.11 (20 mg/kg, three times/week for 2 weeks) exhibited antitumor activity in colony formation and in vivo tumor growth in A375MM xenograft model.