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iMAC2 is the inhibitor of mitochondrial apoptosis-induced channel (MAC) with the IC50 value of 28 nM[1]. MAC is a putative cytochrome c release channel involved in the intrinsic apoptotic pathway. MAC has been associated with oligomeric, not monomeric, Bax[2]. By blocking MAC and suppressing cytochrome c release, iMAC2 suppressed the onset of apoptotic markers [1].

In vitro: In cultured apoptotic FL5.12 cells, pre-treatment with iMAC2 resulted in a normal volume and residual Annexin V/PI staining. iMAC2 reduced apoptosis by more than 50%. Pre-treatment with iMAC2 induced a significant protection at low micromolar levels (IC50 = 2.5 μM). Pre-incubation with iMAC2 and iMAC3 essentially eliminated the release of cytochrome c (P < 0.0001) while nanomolar levels of iMAC2 completely blocked the current flow through MAC. iMAC2 inhibited release of cytochrome c by Bid-induced Bax activation with the IC50 values of 0.68 μM [1].

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