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
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 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 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 . 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.
