| Description | Telcagepant is an orally active antagonist of calcitonin gene-related peptide (CGRP) receptor (Kis: 0.77 nM and 1.2 nM for human and rhesus CGRP receptors, respectively). |
| In vitro | Telcagepant shows affinity (Ki) for the canine and rat receptors, with values of 1204 nM and 1192 nM (n=10), respectively. Telcagepant displays saturable binding to SK-N-MC membranes with a KD of 1.9 nM and Bmax of 479 fmol/mg protein. Telcagepant effectively blocks human α-CGRP-stimulated cAMP responses in the human CGRP receptor-expressing HEK293 cells (IC50: 2.2 nM)[1]. Telcagepant also displays saturable binding to rhesus cerebellum homogenate (KD: 1.3 nM and Bmax of 20 fmol/mg)[2]. |
| In vivo | The pharmacokinetics of Telcagepant (MK-0974) remains linear across 0.5-10 mg/kg intravenous dose in monkeys, but the oral area under the plasma concentration-time curve (AUC) enhances (5-30 mg/kg) is 15-fold over dose-proportional. Telcagepant (i.v. bolus, 1 mg/kg) demonstrates that the efficacy of this antagonist is time-dependent and correlated with plasma levels[1][3]. |
| Target activity | CGRP (human):(ki)0.77 nM, CGRP (rhesus):1.2 nM(ki) |
| Synonyms | MK-0974 |
| molecular weight | 566.52 |
| Molecular formula | C26H27F5N6O3 |
| CAS | 781649-09-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 50 mg/mL (88.26 mM) |
| References | 1. Salvatore CA, 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 Feb;324(2):416-21. Epub 2007 Nov 26. 2. Moore EL, et al. Examining the binding properties of MK-0974: a CGRP receptor antagonist for the acute treatment of migraine. Eur J Pharmacol. 2009 Jan 14;602(2-3):250-4. 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 Jan;39(1):33-45. |