MPT0B392 是一种口服活性的喹啉衍生物，作用于c-Jun N末端激酶 (JNK)和apoptosis的激活剂。MPT0B392 抑制微管蛋白聚合，通过激活 JNK 诱导细胞有丝分裂停滞，线粒体膜电位丧失和caspases裂解，最终导致细胞凋亡。MPT0B392 是一种新型微管解聚剂，可增强西罗莫司对耐药急性白血病细胞和多药耐药细胞系的细胞毒性。
| 生物活性 | MPT0B392, an orally active quinoline derivative, inducesc-Jun N-terminal kinase(JNK)activation, leading toapoptosis. MPT0B392 inhibits tubulin polymerization and triggers induction of the mitotic arrest, followed by mitochondrial membrane potential loss andcaspasescleavage by activation ofJNKand ultimately leads toapoptosis. MPT0B392 is demonstrated to be a novelmicrotubule-depolymerizingagent and enhances the cytotoxicity of sirolimus in sirolimus-resistant acute leukemic cells and the multidrug resistant cell line[1]. |
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体外研究
(In Vitro) | MPT0B392 (B392) (0.001-0.1 μM; 24 and 48 hours) inhibits the cell viability of HL60, MOLT-4, and CCRF-CEM cells with IC50s of 0.02 μM, 0.03 μM and 0.02 μM, respectively[1].
MPT0B392 (0.1 μM; 48 hours) induces apoptosis in HL60 cancer cells[1].
MPT0B392 (0.1 μM for 6-48 hours; 0.01-0.1 μM for 24 and 48 hours) triggers cells arrest in the G2/M phase, followed by accumulation in subG1 phase in a concentration and time-dependent manner[1].
MPT0B392 (0.1 μM; 48 hours) increases the phosphorylation of Bcl-2, Mcl-1S and decreases in Mcl-1L[1].
Cell Viability Assay[1] | Cell Line: | HL60 (acute promyelocytic leukemia), MOLT-4 (acute lymphoblastic leukemia), CCRF-CEM (acute lymphoblastic leukemia) cells | | Concentration: | 0.001, 0.003, 0.01, 0.03, 0.1 μM | | Incubation Time: | 24 and 48 hours | | Result: | Inhibited the cell viability. |
Apoptosis Analysis[1] | Cell Line: | HL60 cells | | Concentration: | 0.1 μM | | Incubation Time: | 48 hours | | Result: | Induced apoptosis in cancer cells. |
Cell Cycle Analysis[1] | Cell Line: | HL60 cells | | Concentration: | 0.1 μM or 0.01, 0.03, 0.1 μM | | Incubation Time: | 0.1 μM for 6-48 hours; 0.01-0.1 μM for 24 and 48 hours | | Result: | Triggered cells arrest in the G2/M phase, followed by accumulation in subG1 phase in a concentration and time-dependent manner. |
Western Blot Analysis[1] | Cell Line: | HL60 cells | | Concentration: | 0.1 μM | | Incubation Time: | 48 hours | | Result: | Increased the phosphorylation of Bcl-2, Mcl-1S and decreased in Mcl-1L. |
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体内研究
(In Vivo) | The effects of MPT0B392 (oral gavage; 50 mg/kg or 100 mg/kg for 12 or 14 days) shows relative potent anti-leukemia activity in a vivo xenograft model[1].
| Animal Model: | Severe combined immunodeficient (SCID) mice[1] | | Dosage: | 50 mg/kg or 100 mg/kg | | Administration: | Oral gavage; 12 or 14 days | | Result: | Resulted in significant tumor growth delay (83.3%) and tumor volume inhibition without loss of body weight. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(247.26 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.4726 mL | 12.3628 mL | 24.7255 mL | | 5 mM | 0.4945 mL | 2.4726 mL | 4.9451 mL | | 10 mM | 0.2473 mL | 1.2363 mL | 2.4726 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (6.18 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (6.18 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 *以上所有助溶剂都可在本网站选购。
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