EAPB0503, a novel imidazoquinoxaline derivative, inhibits growth and induces apoptosis in chronic myeloid leukemia cells.

摘要: Imatinib, the first-generation tyrosine kinase inhibitor, revolutionized therapeutic management of chronic myeloid leukemia (CML) and is highly effective in inducing remissions prolonging survival CML patients. However, one-third patients develop intolerance or resistance to treatment, stem cells remain insensitive this therapy, leading almost inevitably relapse upon treatment discontinuation. Imidazoquinoxalines are imiquimod derivatives that induce growth inhibition induction caspase-dependent apoptosis melanoma T-cell lymphoma cells. We investigated effects EAPB0203 EAPB0503, two novel imidazoquinoxaline derivatives, on human cell lines showed they induced a dose-dependent time-dependent inhibition. EAPB0503 proved more potent specific cycle arrest mitosis direct activation as evidenced by increased pre-G0 population, breakdown mitochondrial membrane potential, PARP cleavage, DNA breakage. Interestingly, decreased BCR-ABL oncoprotein levels. The combination with imatinib synergized inhibit proliferation cells, most importantly, EABP0503 inhibited imatinib-resistant offering promising modalities would circumvent inhibitors improve prognosis CML.