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Maritoclax
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Maritoclax
CAS No. : 1227962-62-0
MCE 站:Maritoclax
产品活性:Maritoclax (Marinopyrrole A) 是一种新颖的 Mcl-1 特异性抑制剂,IC50 值为 10.1 μM,对 BCL-xl 的 IC50 值 > 80 μM。
研究领域:Apoptosis
作用靶点:Bcl-2 Family
In Vitro: Maritoclax (Marinopyrrole A) blocks the binding of Bim BH3 α-helix to Mcl-1 but not Bcl-XL. Maritoclax (Marinopyrrole A) markedly inhibits the viability of Mcl-1-IRES-BimEL cells (EC50=1.6 μM) with a selectivity greater than 40-fold over Bcl-2-IRES-BimEL (EC50=65.1 μM) and Bcl-XL-IRES-BimEL (EC50=70.0 μM) cells. Maritoclax (Marinopyrrole A) induces cell death selectively in Mcl-1-dependent but not Bcl-2- or Bcl-XL-dependent leukemia cells. Maritoclax (Marinopyrrole A) induces proteasome-mediated Mcl-1 degradation without induction of Mcl-1 phosphorylation and Noxa expression. Maritoclax (Marinopyrrole A) inhibits Mcl-1 interaction with Bim in intact cells and triggers cytochrome c release from isolated mitochondria. Maritoclax (Marinopyrrole A) synergistically sensitizes lymphoma/leukemia cells to ABT-737. Maritoclax (Marinopyrrole A) shows activity against all tested S. aureus strains, including glycopeptide-intermediate and vancomycin-resistant MRSA, and has potent activities against other Gram-positive organisms. In addition, Maritoclax (Marinopyrrole A) is active against H. influenzae but is inactive against other tested Gram-negative strains. Maritoclax (Marinopyrrole A) displays substantial concentration-dependent killing against MRSA strain TCH1516 and is far more rapid in its antibiotic action than either vancomycin or linezolid. Maritoclax exhibits a favorable therapeutic index, with 50% inhibitory concentrations (IC50) in excess of 20× above the MIC in each case: 32 to 64 μg/mL against HeLa cells and 8 to 32 μg/mL against L929 cells. Maritoclax (Marinopyrrole A) (3 μM) induced-cell death is associated with MCL1 decrease and translation inhibition. Maritoclax (Marinopyrrole A) induces a dephosphorylation of EIF4EBP1 concomitant to a decrease of EIF4E phosphorylation. Maritoclax (Marinopyrrole A) is much more effective against Bcl-2-dependent RS4;11 cells (IC50: 2 μM) when compared to Mcl-1-dependent HeLa cells (IC50: 20 μM).
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