Maritoclax

Maritoclax, also known as Marinopyrrole A , is a small molecule Mcl-1 inhibitor, which induces Mcl-1 proteasomal degradation without transcriptional downregulation. Maritoclax killed AML cell lines and primary cells with elevated Mcl-1 levels through selective Mcl-1 downregulation, and synergized with ABT-737 to overcome Mcl-1-mediated ABT-737 resistance. Maritoclax was more effective than daunorubicin at inducing leukemic cell death when co-cultured with HS-5 bone marrow stroma cells, while being less toxic than daunorubicin against HS-5 stroma cells, primary mouse bone marrow cells, and hematopoietic progenitor cells. Moreover, maritoclax administration at 20 mg/kg/d intraperitoneally caused significant U937 tumor shrinkage, as well as 36% tumors remission rate in athymic nude mice, without apparent toxicity to healthy tissue or circulating blood cells. In summary, our studies suggest that maritoclax belongs to a novel class of Mcl-1 inhibitors that has the potential to be developed for the treatment of AML. ( Cancer Biol Ther. 2014 Aug;15(8):1077-86. )

ChEBI: (-)-marinopyrrole A is a member of the class of pyrroles that is 1'H-1,3'-bipyrrole substituted by four chloro groups at positions 4, 4', 5 and 5' and two 2-hydroxybenzoyl moieties at positions 2 and 2'. It is isolated from Streptomyces sp.CNQ-418 and exhibits cytotoxic and antibacterial activities. It has a role as an antimicrobial agent, an antibacterial agent, an antineoplastic agent, a marine metabolite and a bacterial metabolite. It is a member of pyrroles, an organochlorine compound, a member of phenols and an aromatic ketone.