MK-3207

MK-3207 is a potent and orally bioavailable CGRP receptor antagonist (IC50= 0.12 nM; Ki value= 0.024 nM); highly selective versus human AM1, AM2, CTR, and AMY3.IC50 Value: 0.024 nM (Ki, Human CGRP) [1]In common with other CGRP receptor antagonists, MK-3207 displays lower affinity for human CGRP receptors from other species, including canine and rodent.in vitro: MK-3207 is a potent antagonist of the human and rhesus monkey CGRP receptors (K(i) = 0.024 nM). in vivo: MK-3207 produced a concentration-dependent inhibition of dermal vasodilation, with plasma concentrations of 0.8 and 7 nM required to block 50 and 90% of the blood flow increase, respectively. The tritiated analog [3H]MK-3207 was used to study the binding characteristics on the human CGRP receptor. [3H]MK-3207 displayed reversible and saturable binding (K(D) = 0.06 nM), and the off-rate was determined to be 0.012 min(-1), with a t(1/2) value of 59 min [1]. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5?mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100?mg) were continued into the second stage [2].Clinical trial: MK-3207 for the treatment of acute migraines. Phase 2b

Signaling Pathways >> GPCR/G Protein >> CGRP Receptor

Signaling Pathways >> Neuronal Signaling >> CGRP Receptor

Research Areas >> Neurological Disease

[1]. Salvatore CA, Moore EL, Calamari A, Pharmacological properties of MK-3207, a potent and orally active calcitonin gene-related peptide receptor antagonist. J Pharmacol Exp Ther. 2010 Apr;333(1):152-60.

[2]. Hewitt DJ, Aurora SK, Dodick DW, Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia. 2011 Apr;31(6):712-22.

Olcegepant | BMS-927711 | MK-0974 | MK-3207 HCl | Calcitonin Gene Related Peptide Fragment 8-37 human | Rat CGRP-(8-37) | Adrenomedullin (22-52) (human) | Ubrogepant | β-CGRP (human)