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。
MPT0B392, an orally active quinoline derivative, induces c-Jun N-terminal kinase (JNK) activation, leading to apoptosis. MPT0B392 inhibits tubulin polymerization and triggers induction of the mitotic arrest, followed by mitochondrial membrane potential loss and caspases cleavage by activation of JNK and ultimately leads to apoptosis. MPT0B392 is demonstrated to be a novel microtubule-depolymerizing agent and enhances the cytotoxicity of sirolimus in sirolimus-resistant acute leukemic cells and the multidrug resistant cell line[1]. JNK Caspase
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
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]
[1]. Chao MW, et al. An oral quinoline derivative, MPT0B392, causes leukemic cells mitotic arrest and overcomes drug resistant cancer cells. Oncotarget. 2017 Apr,8(17):27772-27785.
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