Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1094-1097 |
Number of pages | 4 |
Journal | Investigational New Drugs |
Volume | 29 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2011 |
Keywords
- APcK110
- Acute myeloid leukemia
- Kit inhibitor
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)
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