Maritoclax (Marinopyrrole A) (Marinopyrrole A) is a novel and specific Mcl-1 inhibitor, shows >8 fold selectivity than BCL-xl (IC50 > 80 μM),with an IC50 value of 10.1 μM.

MCL1:10.1 μM

Maritoclax (Marinopyrrole A) (3 µM) induces cell death associated with MCL1 decrease and translation inhibition. It dephosphorylates EIF4EBP1 while reducing EIF4E phosphorylation[3]. Maritoclax is significantly more effective against Bcl-2-dependent RS4;11 cells (IC50: 2 µM) compared to Mcl-1-dependent HeLa cells (IC50: 20 µM)[4]. It blocks Bim BH3 α-helix binding to Mcl-1 but not Bcl-XL, and markedly inhibits the viability of Mcl-1-IRES-BimEL cells (EC50=1.6 µM) with over 40-fold selectivity compared to Bcl-2-IRES-BimEL (EC50=65.1 µM) and Bcl-XL-IRES-BimEL (EC50=70.0 µM) cells. Maritoclax selectively induces cell death in Mcl-1-dependent leukemia cells and causes proteasome-mediated Mcl-1 degradation without inducing Mcl-1 phosphorylation or Noxa expression. It inhibits Mcl-1 interaction with Bim in intact cells, triggers cytochrome c release from isolated mitochondria, and synergistically sensitizes lymphoma/leukemia cells to ABT-737[1]. Maritoclax is active against all tested S. aureus strains, including glycopeptide-intermediate and vancomycin-resistant MRSA, and has potent activity against other Gram-positive organisms, and H. influenzae but is inactive against tested Gram-negative strains. It shows substantial concentration-dependent killing against MRSA strain TCH1516 and acts more rapidly than vancomycin or linezolid. Maritoclax exhibits a favorable therapeutic index with IC50 values exceeding 20× above the MIC: 32–64 µg/mL against HeLa cells and 8–32 µg/mL against L929 cells[2].