Marinopyrrole A (Maritoclax)

製品コードS7126 バッチS712602

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H12Cl4N2O4
分子量 510.15 CAS No. 1227962-62-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (196.02 mM)
Ethanol 59 mg/mL (115.65 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 K562 cells
濃度 2 μM
反応時間 12 h
実験の流れ

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.
動物実験 動物モデル Female athymic nude (NCI Athymic NCr-nu/nu 01B74) mice
投薬量 20 mg/kg
投与方法 i.p.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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