Marinopyrrole A (Maritoclax)

Catalog No.S7126 Batch:S712601

Technical Data

Formula	C₂₂H₁₂Cl₄N₂O₄
Molecular Weight	510.15	CAS No.	1227962-62-0
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (196.02 mM)
		Ethanol	45 mg/mL (88.2 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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

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].

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].

Protocol (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[3]}	Animal Models Female athymic nude (NCI Athymic NCr-nu/nu 01B74) mice Dosages 20 mg/kg Administration i.p.

Cell Assay:^{^[1]}

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.

Animal Study:^{^[3]}

Animal Models
Female athymic nude (NCI Athymic NCr-nu/nu 01B74) mice
Dosages
20 mg/kg
Administration
i.p.

References

Selleck's Marinopyrrole A (Maritoclax) has been cited by 4 publications

Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies [ Clin Cancer Res, 2023, 29(2):446-457]	PubMed: 36346691
PHLPP1 deficiency ameliorates cardiomyocyte death and cardiac dysfunction through inhibiting Mcl-1 degradation [ Cell Signal, 2022, S0898-6568(22)00041-9]	PubMed: 35151832
The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL [Kampen KR, et al. Leukemia, 2019, 33(2):319-332]	PubMed: 29930300
Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP [ Molecules, 2018, 23(11)E3030]	PubMed: 30463333

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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