产品说明书

MK-3207

Print
Chemical Structure| 957118-49-9 同义名 : -
CAS号 : 957118-49-9
货号 : A346165
分子式 : C31H29F2N5O3
纯度 : 98%
分子量 : 557.591
MDL号 : MFCD16038933
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 145 mg/mL(260.05 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide involved in the pathophysiology of migraine. MK-3207 is a potent, orally bioavailable CGRP receptor antagonist. It exhibited high affinity for recombinant human receptor and for native human CGRP receptor in SK-N-MC cells with Ki values of 0.022 and 0.024nM, respectively. MK-3207 also displayed a similar affinity for rhesus monkey receptor with a Ki value of 0.024nM. In HEK293 cells expressing human CGRP receptor, MK-3207 inhibited human α-CGRP-stimulated cAMP responses with an IC50 value of 0.12±0.02nM. MK-3207 dose-dependently inhibited capsaicin-induced dermal blood flow in the rhesus monkey forearm with EC50 and EC90 values of 0.8 and 7nM, respectively. The IC50 value of MK-3207 in the human serum-shifted in vitro functional assay was 17nM[3].
作用机制 MK-3207 is a potent, highly selective, and orally bioavailable antagonist of human and rhesus monkey CGRP receptors. The receptor activity-modifying protein 1 (RAMP1) is a transmembrane-spanning protein responsible for the regulation of CGRP activity. The residue 74 on RAMP1 plays a key role in MK-3207 binding to CGRP receptor.
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00712725 - Completed - -
NCT00548353 Migraine Disorders Phase 1 Completed - -
NCT00712725 Migraine Phase 2 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.79mL

0.36mL

0.18mL

8.97mL

1.79mL

0.90mL

17.93mL

3.59mL

1.79mL
参考文献

[1]Hewitt DJ, Aurora SK, et al. 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, et al. 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.

[3]Salvatore CA, Moore EL, Calamari A, Cook JJ, Michener MS, O'Malley S, Miller PJ, Sur C, Williams DL Jr, Zeng Z, Danziger A, Lynch JJ, Regan CP, Fay JF, Tang YS, Li CC, Pudvah NT, White RB, Bell IM, Gallicchio SN, Graham SL, Selnick HG, Vacca JP, Kane SA. 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. doi: 10.1124/jpet.109.163816. Epub 2010 Jan 11. PMID: 20065019.