產(chǎn)品目錄

規(guī)格	10mg 50mg 100mg
CAS	781649-09-0
別名	Telcagepant;MK0974;MK 0974
化學(xué)名	N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide
分子式	C26H27F5N6O3
分子量	566.54
溶解度	DMSO: 10 mM,Ethanol: 1 mg/ml
儲存條件	Store at -20°C
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request

產(chǎn)品描述：

MK-0974 (Telcagepant) is a highly potent, selective, and orally bioavailable antagonist of CGRP receptor with IC50 value of 0.77 nM [1].

Calcitonin gene-related peptide (CGRP) receptor is a heteromeric transmembrane receptor composed of a G protein-coupled receptor which is called calcitonin receptor-like receptor (CALCRL) and a receptor activity modifying protein 1 (RAMP1). CGRP receptor is functional for mediating the activity of CGRP, which is widely distributed in human peripheral and central neuron system. The CGRP/CGRP receptor signaling pathway modulate a variety of physiological functions of respiratory, immune and cardiovascular system, and play a key role in the pathophysiology of migraine headache.

When binding study was carried out, it was found MK-0974 had high affinity for CGRP receptor but had no affinity for related human adrenomedullin receptors, which suggested the high specificity of MK-0974 [1]. In human HEK293 cells expressing CGRP receptor, treatment of MK-0974 resulted in potent blockage of α-CGRP-stimulated cAMP producation, which indicated a significant inhibition of CGRP receptor activity. However, addition of 50% human serum reduced the inhibition potency of MK-0974 by 5-fold [1]. MK-0974 displayed reversible and saturable binding to both SK-N-MC membranes and rhesus cerebellum with a Kd of 1.9 nM and 1.3 nM, respectively [2].

In rhesus model, capsaicin-induced release of endogenous CGRP resulted in dermal vasodilation. Following treatment of MK-0974 produced a dose-dependent inhibition of dermal vasodilation, with plasma concentrations of 127 and 994 nM required to block 50 and 90% of the blood flow increase, respectively. The suppression of CGRP function indicated the inhibition of CGRP receptor by MK-0974 [1]. In monkey model, MK-0974 showed moderate clearance (14-20 ml min-1 kg-1), while oral bioavailability was 6%. The pharmacokinetics of MK-0974 remained linear across 0.5-10 mg kg-1 intravenous dose in monkeys, but the oral area under the plasma concentration-time curve (AUC) increase (5-30 mg kg-1) was 15-fold over dose-proportional [3].

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1. 本產(chǎn)品僅供科研使用。請勿用于醫(yī)藥、臨床診斷或治療，食品及化妝品等用途。請勿存放于普通住宅區(qū)。

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原創(chuàng)作者：上海莼試生物技術(shù)有限公司

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