BMS-694153 is a potent, selective calcitonin gene-related peptide (CGRP) receptor antagonist with Ki of 0.013 nM for hCGRP (inhibition of 125I-CGRP binding in SK-N-MC cell membranes).
BMS-694153 is a full, competitive antagonist, potently inhibits CGRP-stimulated cAMP production in SK-N-MC cells with EC50 of 0.0345 nM.
BMS-694153 show species-specific differences with relatively poor activity against nonprimate receptors, shows no inhibition of CGRP binding to the rat receptor at 1 uM.
BMS-694153 displays >10000-fold selectivity for CGRP over adrenomedullin receptors 1 and 2, calcitonin, and amylin receptors 1 and 3.
BMS-694153 shows no significant potential for off-target liabilities in a broad panel of receptor and ion channel binding and enzyme activity assays.
BMS-694153 potently reverses CGRP-induced dilation with EC50 of 0.06 nM in ex vivo human intracranial arteries.
BMS-694153 has good intranasal bioavailablity in rabbits and shows dose-dependent activity in validated in vivo and ex vivo migraine models.