MK-3207 Hydrochloride

• CAT Number: I005674
• CAS Number: 957116-20-0
• Molecular Formula: C31H29F2N5O3.HCl
• Molecular Weight: 594.05
• Purity: ≥95%
• Synonyms: MK-3207；MK3207；
• Target: CGRP
• Solubility: DMSO ≥114mg/mL Water ≥4.6mg/mL Ethanol ≥115mg/mL
• Storage: 3 years -20C powder
• IC50: 0.024 nM (Ki, Human CGRP)

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. 


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, 5mg) 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, 100mg) were continued into the second stage [2]. 


Clinical trial: MK-3207 for the treatment of acute migraines. Phase 2b

Reference

[1]. 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. 


[2]. 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.