AAL-993 is a potent inhibitor of VEGF receptors, inhibiting VEGFR1, 2, and 3 with IC50 values of 130, 23, and 18 nM, respectively. It less potently inhibits c-Kit, colony stimulating factor 1 receptor, PGDF receptor β, and EGF receptor (IC50s = 236, 380, 640, and 1,040 nM, respectively) and is without effect on a number of other tyrosine kinases. AAL-993 is orally bioavailable in vivo, blocks VEGF-induced angiogenesis, and prevents the growth of primary tumors and spontaneous peripheral metastases in mice. It also inhibits hypoxia-mediated increase in hypoxia-inducible factor-1 transcriptional activity in an ERK-dependent manner (IC50 = ~5 μM).
