（±）-Marinopyrrole A (C09-0967-555)

InformationMarinopyrrole A (Maritoclax) Marinopyrrole A (Maritoclax) is a selective Mcl-1 antagonist. It binds to Mcl-1, but not Bcl-XL, and targets Mcl-1 for proteasomal degradation. Maritoclax disrupts the interaction between Bim and Mcl-1 with an IC50 of 10.1 μM.TargetsMcl-1In vitroMaritoclax induces Mcl-1 degradation via the proteasome system, which is associated with the pro-apoptotic activity of maritoclax. Maritoclax 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 μM. Maritoclax blocks the interaction between a biotin-labeled Bim-BH3 peptide and GST-Mcl-1 in a dose-dependent manner with an IC50 value of 10.1 μM, while it does not inhibit the binding of Bim-BH3 peptide to GST-Bcl-XL at concentrations up to 80 μM. Maritoclax induces caspase-3 activation by degradation of Mcl-1 protein. Treatment with maritoclax markedly reduces the half-life of Mcl-1 to ∼0.5 h as compared with nearly 3 h in control cells. Maritoclax has no apparent effect on Mcl-1 (Ser159/Thr163) phosphorylation, suggesting that maritoclax induces phosphorylation-independent Mcl-1 degradation. Marinopyrrole A has potent concentration-dependent bactericidal activity against clinically relevant hospital- and community-acquired MRSA strains. Marinopyrrole A shows limited toxicity to mammalian cell lines (at >20× MIC). Maritoclax sensitivity is cell type specific. It is not effective in HeLa, HEK293, or MEF cells. Maritoclax is not a substrate for p-gp mediated drug efflux.In vivoMaritoclax administration at 20 mg/kg/d intraperitoneally causes 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.Cell Research(from reference)Cell lines：K562 cells Concentrations：2 μM Incubation Time：12 h. Specification: 0.98 Molecular Formula: C22H12Cl4N2O4 Molecular Weight: 510.15 PubChem CID: 24797083 Isomeric SMILES: C1=CC=C(C(=C1)C(=O)C2=CC(=C(N2C3=C(NC(=C3Cl)Cl)C(=O)C4=CC=CC=C4O)Cl)Cl)O Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/M413711-SCI_bfc2579b9a7816fc66b634e5317247ad.pdf