[CAS NO. 1227962-62-0] Maritoclax
PRODUCTS SPECIFICATIONS [1227962-62-0]
DESCRIPTION [1227962-62-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 510.15 |
| Molecular Formula | C22H12Cl4N2O4 |
| SMILES | OC1=CC=CC=C1C(C2=C(N3C(C(C4=CC=CC=C4O)=O)=CC(Cl)=C3Cl)C(Cl)=C(Cl)N2)=O |
5 Publications Citing Use of MCE
Summary
IC50 & Target
|
Mcl-1 10.1 μM (IC 50 ) |
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 (EC 50 =1.6 μM) with a selectivity greater than 40-fold over Bcl-2-IRES-BimEL (EC 50 =65.1 μM) and Bcl-XL-IRES-BimEL (EC 50 =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 [1] . 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 (IC 50 ) 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 [2] . 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 [3] . Maritoclax (Marinopyrrole A) is much more effective against Bcl-2-dependent RS4;11 cells (IC 50 : 2 μM) when compared to Mcl-1-dependent HeLa cells (IC 50 : 20 μM) [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 43 mg/mL ( 84.29 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9602 mL | 9.8010 mL | 19.6021 mL |
| 5 mM | 0.3920 mL | 1.9602 mL | 3.9204 mL |
| 10 mM | 0.1960 mL | 0.9801 mL | 1.9602 mL |
References
- [1] Doi K, et al. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012 Mar 23;287(13):10224-35.
- [2] Haste NM, et al. Pharmacological properties of the marine natural product marinopyrrole A against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011 Jul;55(7):3305-12.
- [3] Gomez-Bougie P, et al. The selectivity of Marinopyrrole A to induce apoptosis in MCL1high BCL2low expressing myeloma cells is related to its ability to impair protein translation. Br J Haematol. 2016 Aug 14.
- [4] Eichhorn JM, et al. Purported Mcl-1 inhibitor marinopyrrole A fails to show selective cytotoxicity for Mcl-1-dependent cell lines. Cell Death Dis. 2013 Oct 24;4:e880