AST-487

AST-487 is an inhibitor of RET (IC₅₀ = 0.88 µM), FLT3 (K_i = 0.52 µM), KDR (IC₅₀ = 0.17 µM), c-Abl (IC₅₀ = 0.02 µM), and c-Kit (IC₅₀ = 0.5 µM).^1,2 It has been shown to inhibit RET autophosphorylation and activation of downstream effectors and to prevent the growth of human thyroid cancer cell lines with activating mutations of RET but not of lines without RET mutations.¹ In xenografts of NIH3T3 cells expressing oncogenic RET and of the MTC cell line TT in nude mice, AST-487 dose dependently inhibited tumor growth.¹ It also demonstrates antiproliferative effects on primary cells from acute myelocytic leukemia patients and on cell lines expressing FLT3-ITD or FLT3 kinase domain point mutants.¹

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1. Akeno-Stuart, N., Croyle, M., Knauf, J.A., et al. The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 67(14), 6956-6964 (2007).

2. Weisberg, E., Roesel, J., Bold, G., et al. Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells. Blood 112(13), 5161-5170 (2008).