A non-selective calcium channel blocker
Carboxyamidotriazole is an orally bioavailable, non-selective calcium channel blocker.1 It blocks L- and T-type calcium channels in GH3 rat pituitary cancer cells (IC50s = 0.5 and 1.5 μg/ml, respectively). It also inhibits calcium influx stimulated by the acetylcholine receptor agonist carbachol and the calcium ionophore A23187 in CHO cells expressing human recombinant muscarinic M5 receptors (IC50s = 935 and 359 nM, respectively).2 Carboxyamidotriazole inhibits the growth of T. gondii in non-cancerous human fibroblasts and HeLa human cervical cancer cells (IC50 = 0.06 μg/ml for both).3 It inhibits the growth of FaDu and EVSCC17M human squamous cell carcinoma cells (IC50s = 13 and 15 μM, respectively) and of human umbilical vein endothelial cells (HUVECs; IC50 = 1 μM) in vitro.4,5 Carboxyamidotriazole (20 μM) also inhibits angiogenesis in a chicken chorioallantoic membrane assay in vivo.5
1.Hupe, D.J., Boltz, R., Cohen, C.J., et al.The inhibition of receptor-mediated and voltage-dependent calcium entry by the antiproliferative L-651,582J. Biol. Chem.266(16)10136-10142(1991) 2.Felder, C.C., Ma, A.L., Liotta, L.A., et al.The antiproliferative and antimetastatic compound L651582 inhibits muscarinic acetylcholine receptor-stimulated calcium influx and arachidonic acid releaseJ. Pharmacol. Exp. Ther.257(3)967-971(1991) 3.Hupe, D.J., Pfefferkorn, E.R., Behrens, N.D., et al.L-651,582 inhibition of intracellular parasitic protozoal growth correlates with host-cell directed effectsJ. Pharmacol. Exp. Ther.256(2)462-467(1991) 4.Wu, Y., Palad, A.J., Wasilenko, W.J., et al.Inhibition of head and neck squamous cell carcinoma growth and invasion by the calcium influx inhibitor carboxyamido-triazoleClin. Cancer Res.3(11)1915-1921(1997) 5.Kohn, E.C., Alessandro, R., Spoonster, J., et al.Angiogenesis: Role of calcium-mediated signal transductionProc. Natl. Acad. Sci. USA92(5)1307-1311(1995)
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