MK-3207
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
MK-3207是一种新型的CGRP受体高度选择性拮抗剂,比Telcagepant对人CGRP受体的作用强约40 ~ 65倍。IC50值为0.12 nM;Ki值为0.024 nM。MK-3207对人AM1、AM2、CTR和AMY3具有高度选择性[1]。
降钙素基因相关肽(CGRP)是含37个氨基酸的神经肽,广泛分布于中枢和外周神经系统。CGRP受体由降钙素受体样受体(CLR)、B家族G蛋白耦联受体(GPCR)、受体活性修饰蛋白1(RAMP1)以及受体组分蛋白组成。大量证据表明,CGRP参与偏头痛病理生理过程,因而,CGRP受体拮抗剂有望成为治疗偏头痛的新型药物[2]。
MK-3207与125I-hCGRP竞争结合SK-N-MC细胞的天然人CGRP受体以及重组人受体,显示出较高的亲和力,其Ki值分别为0.024 ± 0.001 nM和0.022 ± 0.002 nM。MK-3207对恒河猴受体(0.024 ± 0.001 nM)和人受体具有相近的亲和力(Ki),对犬和大鼠受体的亲和力则低400倍(相应Ki值为10 nM和10 ± 1.2 nM)。在表达人CGRP受体的HEK293细胞中,MK-3207有效阻断人α-CGRP诱导的cAMP应答,其IC50值为0.12 ±0.02 nM。加入50%的人血清(IC50 =0.17 ± 0.02 nM)几乎不影响MK-3207的作用[3]。
MK-3207抑制猕猴CIDV,其EC50和Emax值约为0.8 ± 0.3 nM(平均值 ± S.E.)和81 ± 5%(平均值 ± S.E.)。因此,恒河猴的预期EC90值约为7 nM(比估计的EC50值高9倍)。口服给予10 mg/kg的MK-3207后,其在脑脊液与血浆中的浓度比为2% ~ 3%。然而,脑脊液/血浆比率约为血浆非结合型分数(9.4%)的30%,这表明中枢和外周隔室没有达到自由平衡。
参考文献:
[1] David J Hewitt, Sheena K Aurora, David W Dodick et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 31(6) 712–722.
[2] Ian M. Bell, Steven N. Gallicchio, Michael R. Wood et al. Discovery of MK-3207: A Highly Potent, Orally Bioavailable CGRP Receptor Antagonist. ACS Med. Chem. Lett. 2010, 1, 24–29.
[3] Christopher A. Salvatore, Eric L. Moore, Amy Calamari, Jacquelynn J. Cook, et al. Pharmacological Properties of MK-3207, a Potent and Orally Active Calcitonin Gene-Related Peptide Receptor Antagonist. doi:10.1124/jpet.109.163816.
Storage | Store at -20°C |
M.Wt | 557.59 |
Cas No. | 957118-49-9 |
Formula | C31H29F2N5O3 |
Synonyms | MK3207;MK 3207 |
Solubility | Soluble in DMSO |
Chemical Name | 2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxospiro[1,3-dihydroindene-2,3'-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide |
SDF | Download SDF |
Canonical SMILES | C1CCC2(C1)C(=O)N(C(CN2)C3=CC(=CC(=C3)F)F)CC(=O)NC4=CC5=C(CC6(C5)C7=C(NC6=O)N=CC=C7)C=C4 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
Description | MK-3207是高度有效的和具有口服生物利用度的CGRP受体拮抗剂,其IC50值为0.12 nM。 | |||||
靶点 | CGRP | |||||
IC50 | 0.12 nM |