Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor characterized by an abnormal proliferation of myeloid progenitor cells, decreased rate of self-destruction and an arrest in cell differentiation. The internal tandem duplication mutations of FMS-like tyrosine kinase-3 (FLT3/ITD mutations) are common in AML and linked to poor prognosis. ITRI-260 generated from designed by computer-assisted rationale drug design and in silico prioritized approaches, was proved to be a potent cell growth inhibitor against FLT3/ITD mutated AML cells through FLT3 and c-Kit inhibition. The in vivo efficacy of ITRI-260 via oral route was demonstrated in MV4-11 xenograft mice model. Besides, two more orthotopic murine models were used to assess the in vivo therapeutic efficacy of ITRI-260. The first one is MV4-11 cell orthotopically engraft into NOD/SCID mice bone marrow and the second one is primary AML cells from AML patient engraft into NOD/SCID mice bone marrow. The results show that ITII-260 can decrease FLT3/ITD mutant leukemia blasts in peripheral blood and bone marrow in both animal models. Finally, ITRI-260 prolongs the survival in both bone marrow engraft mice models. These findings strongly suggest clinical benefits of ITRI-260 in patients with FLT3/ITD AML. Currently we are planning the bridged projects to push ITRI-260 toward IND status.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-160.