MK-0974

SKU: orb2655637

Description

A potent, selective, orally bioavailable CGRP receptor antagonist with Ki of 0.77 nM; shows >10,000-fold selectivity in a panel of assays representing over 160 receptors, transporters, and enzymes; inhibits CGRP-stimulated cAMP production in E10 cells with IC50 of 2.2 nM; inhibits the capsaicin-induced increase in dermal blood flow in monkey models.Migraine Phase 3 Discontinued.

Key Properties

• CAS Number: 781649-09-0
• MW: 566.523
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₇F₅N₆O₃
• SMILES: O=C(N1CCC(N(C2=CC=CN=C2N3)C3=O)CC1)N[C@H]4C(N(CC(F)(F)F)C[C@H](C5=CC=CC(F)=C5F)CC4)=O
• Target: CGRP Receptor
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Telcagepant (MK-0974) (i. v. bolus, 1 mg/kg) demonstrates that the efficacy of this antagonist is time-dependent and correlated with plasma levels. 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) increase (5-30 mg/kg) is 15-fold over dose-proportional.
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• In Vitro:
  Telcagepant (MK-0974) displays affinity (Ki) for the canine and rat receptors, with values of 1204 nM and 1192 nM (n=10), respectively. Telcagepant (MK-0974) potently blocks human α-CGRP-stimulated cAMP responses in human CGRP receptor expressing HEK293 cells with an IC50 of 2.2 nM. Telcagepant (MK-0974) displays saturable binding to SK-N-MC membranes with a KD of 1.9 nM and Bmax of 479 fmol/mg protein. Telcagepant (MK-0974) also displays saturable binding to rhesus cerebellum homogenate with a KD of 1.3 nM and Bmax of 20 fmol/mg.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Telcagepant

Quick Database Links

Gene Symbol

CGRP Receptor