Description
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 lineIn VitroMPT0B392 (B392) (0.001-0.1 µM; 24 and 48 hours) inhibits the cell viability of HL60, MOLT-4, and CCRF-CEM cells with IC 50 s of 0.02 µM, 0.03 µM and 0.02 µM, respectively. MPT0B392 (0.1 µM; 48 hours) induces apoptosis in HL60 cancer cells. 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. MPT0B392 (0.1 µM; 48 hours) increases the phosphorylation of Bcl-2, Mcl-1S and decreases in Mcl-1L. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell 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 AnalysisCell Line: HL60 cells Concentration: 0.1 µM Incubation Time: 48 hours Result: Induced apoptosis in cancer cells. Cell Cycle AnalysisCell 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 AnalysisCell 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.In VivoThe 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Severe combined immunodeficient (SCID) mice 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.IC50& Target:JNK Caspase