Toggle Nav
Close
  • Menu
  • Setting

MK-0974

Catalog No.
A3612
CGRP receptor antagonist
Grouped product items
SizePriceStock Qty
2mg
$105.00
Ship with 10-15 days
5mg
$189.00
Ship with 10-15 days
10mg
$320.00
Ship with 10-15 days
50mg
$1,050.00
Ship with 10-15 days
For scientific research use only and should not be used for diagnostic or medical purposes.

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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].

References:
[1] Salvatore C A et al. , Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther. 2008, 324(2): 416-421.
[2] Moore E L et al. , Examining the binding properties of MK-0974: a CGRP receptor antagonist for the acute treatment of migraine. Eur J Pharmacol. 2009, 602(2-3): 250-254.
[3].  Roller S et al., Preclinical pharmacokinetics of MK-0974, an orally active calcitonin-gene related peptide (CGRP)-receptor antagonist, mechanism of dose dependency and species differences. Xenobiotica. 2009, 39(1): 33-45.

Chemical Properties

StorageStore at -20°C
M.Wt566.54
Cas No.781649-09-0
FormulaC26H27F5N6O3
SynonymsTelcagepant;MK0974;MK 0974
SolubilitySoluble in DMSO
Chemical NameN-[(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
SDFDownload SDF
Canonical SMILESC1CC(C(=O)N(CC1C2=C(C(=CC=C2)F)F)CC(F)(F)F)NC(=O)N3CCC(CC3)N4C5=C(NC4=O)N=CC=C5
Shipping ConditionSmall Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips We do not recommend long-term storage for the solution, please use it up soon.

Biological Activity

Description MK-0974(Telcagepant) is a highly potent, selective, and orally bioavailable antagonist of CGRP receptor with Ki values of 0.77 nM and 1.2 nM for human and rhesus CGRP receptors respectively.
Targets CGRP receptor          
IC50 0.77 nM and 1.2 nM (Human and rhesus CGRP,Ki)          

Quality Control

Quality Control & MSDS

View current batch:

Chemical structure

MK-0974