BAX activation inhibitor 1 (BAI1) demonstrates inhibition of tBID-induced BAX-mediated membrane permeabilization in a dose dependent manner with an IC50 of 3.3 μM. BAI1 binds to monomeric BAX at a novel allosteric site. BAI1 is a potent inhibitor of BAX conformational activation and oligomerization in solution, not by direct competition with the activator, but rather through an allosteric mechanism that favors the inactive BAX. Moreover, BAI1 inhibited BAX membrane association and translocation induced either by tBID (IC50 = 5 ± 1 μΜ) or BIM SAHB (IC50 = 2 ± 1 μΜ) in a dose dependent manner and with a similar IC50 to BAX-mediated liposomal release. BAI1 selectively inhibits BAX-dependent cell death.
