AAL-993

AAL-993 is a potent inhibitor of VEGF receptors, inhibiting VEGFR1, 2, and 3 with IC₅₀ values of 130, 23, and 18 nM, respectively.^1,2 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.¹ AAL-993 is orally bioavailable in vivo, blocks VEGF-induced angiogenesis, and prevents the growth of primary tumors and spontaneous peripheral metastases in mice.^1,3 It also inhibits hypoxia-mediated increase in hypoxia-inducible factor-1 transcriptional activity in an ERK-dependent manner (IC₅₀ = ~5 µM).⁴

WARNING This product is not for human or veterinary use.

1. Manley, P.W., Furet, P., Bold, G., et al. Anthranilic acid amides: A novel class of antiangiogenic VEGF receptor kinase inhibitors. J. Med. Chem. 45(26), 5687-5693 (2002).

2. Honda, T., Tajima, H., Kaneko, Y., et al. Conformation-activity relationship on novel 4-pyridylmethylthio derivatives with antiangiogenic activity. Bioorg. Med. Chem. Lett. 18(9), 2939-2943 (2008).

3. Manley, P.W., Bold, G., Brüggen, J., et al. Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis. Biochim. Biophys. Acta 1697(1-2), 17-27 (2004).

4. Ban, H.S., Uno, M., and Nakamura, H. Suppression of hypoxia-induced HIF-1α accumulation by VEGFR inhibitors: Different profiles of AAL993 versus SU5416 and KRN633. Cancer Lett. 296(1), 17-26 (2010).