product name MK-3207 HCl
Description: MK-3207 is a potent and orally active CGRP receptor antagonist with IC50 and Kiof 0.12 nM and 0.022 nM, it is highly selective versus human AM1, AM2, CTR, and AMY3. MK 3207 exhibits significantly higher affinity for both native and recombinant human CGRP receptor, as well as rhesus monkey CGRP receptor with Ki of 24 pM, ~24 pM and 22 pM, respectively, as compared to CGRP receptors from other species, including canine and rodent (Ki values of ~10 nM).
References: J Pharmacol Exp Ther. 2010 Apr;333(1):152-60.
594.05
Formula
C31H29F2N5O3.HCl
CAS No.
957116-20-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 119 mg/mL (200.3 mM)
Water: 5 mg/mL (8.4 mM)
Ethanol: 119 mg/mL (200.3 mM)
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19406833
| In Vitro |
In vitro activity: MK 3207 exhibits significantly higher affinity for both native and recombinant human CGRP receptor, as well as rhesus monkey CGRP receptor with Ki of 24 pM, ~24 pM and 22 pM, respectively, as compared to CGRP receptors from other species, including canine and rodent (Ki values of ~10 nM). Although has affinity for AMY1 (CTR/RAMP1) receptor with a Ki value of 0.75 nM, MK 3207 displays marked selectivity for human CGRP receptor versus related human AM1 (CLR/RAMP2) receptor, AM2 (CLR/RAMP3) receptor, AMY3 (CTR/RAMP3) receptor, and CTR with Ki values of 16.5 μM, 0.156 μM, 0.128 μM and 1.9 μM, respectively. MK 3207 potently inhibits human α-CGRP-induced cAMP production in HEK293 cells stably expressing human CLR/RAMP1 with an IC50 of 0.12 nM, and maintains similar potency in the presence of 50% human serum with an IC50 of 0.17 nM, indicating that the activity of MK 3207 would not be dramatically affected by plasma protein binding in vivo. MK 3207 exhibits approximately 65-fold more potent in the human serum-shifted in vitro functional assay than telcagepant with an IC50 of 10.9 NM. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Administration of MK 3207 produces a concentration-dependent inhibition of capsaicin-induced dermal vasodilation in rhesus monkeys, blocking the blood flow increase with an EC50 of 0.8 nM and an EC90 of 7 nM, respectively. MK 3207 displays approximately 100-fold more potent in the rhesus monkey CIDV assay versus telcagepant with an EC90 of 994 NM. |
| Animal model | Adult rhesus monkeys (either sex) with capsaicin-induced dermal vasodilation |
| Formulation & Dosage | Dissolved in DMSO; 123.1 μg/kg; i.v. |
| References | J Pharmacol Exp Ther. 2010 Apr;333(1):152-60. |
