Erschienen in:
01.10.2011 | SHORT REPORT
Kit inhibitor APcK110 extends survival in an AML xenograft mouse model
verfasst von:
Stefan Faderl, Carlos Bueso-Ramos, Zhiming Liu, Ashutosh Pal, William Bornmann, Diana V. Ciurea, David Harris, Inbal Hazan-Halevy, Hagop M. Kantarjian, Zeev Estrov
Erschienen in:
Investigational New Drugs
|
Ausgabe 5/2011
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Summary
Background: Constitutive activation of kit contributes to pathogenesis of acute myeloid leukemia (AML) and targeting Kit may be of therapeutic benefit. APcK110, a novel inhibitor of Kit, has potent proapoptotic and antiproliferative activity in AML cell lines and primary AML samples. Here we extend our studies to the activity of APcK110 in a xenograft mouse model. Methods: After sub-lethal whole body radiation, OCI/AML3 cells were injected intravenously in NOD-SCID mice. Ten days later, either APcK110 or phosphate buffered saline (PBS) was injected intraperitoneally every other day. Kaplan-Meier estimates were used to calculate survival. Results: We show that 1) all mice injected with OCI/AML3 cells developed a clinical and histological picture consistent with myelomonocytic AML; and 2) survival of APcK110-treated mice was significantly longer compared with mice injected with PBS (p = .02). Conclusions: APcK110 is a novel kit kinase inhibitor with anti-AML activity in vitro and in vivo. Further evaluation in toxicology and clinical studies is warranted.