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Acute myelogenous leukemia (AML)

FMS-like tyrosine kinase 3 (FLT3; CD135); aurora kinases

In vitro and mouse studies identified inhibitors of aurora kinases and FLT3 that could help treat AML. In enzymatic assays, an optimized imidazole[4,5-b]pyridine-based compound inhibited activity of aurora kinases and FLT3 with nanomolar KD values. In mice with mutant FLT3-expressing human AML xenografts, oral treatment with the inhibitor blocked tumor growth and caused tumor regression, whereas vehicle treatment did not. Ongoing work includes additional preclinical formulation and toxicology studies.
At least nine companies have FLT3 inhibitors in clinical and preclinical testing to treat cancers.

SciBX 5(43); doi:10.1038/scibx.2012.1132
Published online Nov. 1, 2012

Covered by issued and filed patent applications; unavailable for licensing

Bavetsias, V. et al. J. Med. Chem.; published online Oct. 8, 2012;
Contact: Julian Blagg, The Institute of Cancer Research, London, U.K.