Home Apoptosis Bcl-2 antagonist Marinopyrrole A (Maritoclax) For research use only.

Marinopyrrole 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.

Marinopyrrole A (Maritoclax) Chemical Structure

Marinopyrrole A (Maritoclax) Chemical Structure

CAS No. 1227962-62-0

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Marinopyrrole A (Maritoclax) Related Products

Signaling Pathway

Bcl-2 Signaling Pathways

Bcl-2 Signaling Pathway

Biological Activity

Description 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.
Targets
Mcl-1 [1]
In vitro
In vitro Maritoclax 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[1]. 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)[2]. 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[3].
Cell Research Cell lines K562 cells
Concentrations 2 μM
Incubation Time 12 h
Method

K562 cells expressing Mcl-1-IRES-BimEL are treated with DMSO, 2 μM maritoclax alone, or in combination with 1 μM MG132 for 12 h. Cells are lysed in 1% Chaps buffer (1% Chaps, 150 mM NaCl, 10 mM Hepes, pH7.4) containing protease inhibitors. Cell lysates containing 350 μg of protein are incubated with 4 μl of rabbit anti-Mcl-1 antiserum or control pre-immune serum in 250 μl of the same lysis buffer at 4 °C overnight on a rotator. Immunoprecipitates are collected by adding 20 μl of protein A-Sepharose beads for 3 h at 4 °C, followed by centrifugation at 6,000 rpm for 30 s. The beads are washed five times with the same lysis buffer, boiled for 5 min in Laemmli sample buffer and analyzed by Western blotting.
In Vivo
In vivo Maritoclax 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[3].
Animal Research Animal Models Female athymic nude (NCI Athymic NCr-nu/nu 01B74) mice
Dosages 20 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 510.15 Formula

C22H12Cl4N2O4
CAS No. 1227962-62-0 SDF Download Marinopyrrole A (Maritoclax) SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (196.02 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 59 mg/mL

Water : Insoluble


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In vivo
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