marinopyrrole-a

Description: Marinopyrrole A (also known as Maritoclax) is a natural product and a selective antagonist of Mcl-1, a protein of the anti-apoptotic Bcl-2 family which including Bcl-2, Bcl-X(L) and Mcl-1, and are well-validated drug targets for cancer treatment. Marinopyrrole A can overcome ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation, while ABT-737 and its orally active analog ABT-263 are the most potent and specific inhibitors to date that bind Bcl-2 and Bcl-X(L) with high affinity but have a much lower affinity for Mcl-1, they are not very effective as single agents in certain cancer types because of elevated levels of Mcl-1. Maritoclax disrupts the interaction between Bim and Mcl-1 with an IC50 of 10.1 uM. Marinopyrrole A induces Mcl-1 degradation via the proteasome system, which is associated with the pro-apoptotic activity of maritoclax. Marinopyrrole A selectively kills Mcl-1-dependent, but not Bcl-2- or Bcl-XL-dependent, leukemia cells and markedly enhances the efficacy of ABT-737 against hematologic malignancies, including K562, Raji, and multidrug-resistant HL60/VCR, by ?60- to 2000-fold at 1-2 uM.

References: J Biol Chem. 2012 Mar 23; 287(13):10224-35; Antimicrob Agents Chemother. 2011 Jul; 55(7):3305-12.