1. GPCR/G Protein
    Neuronal Signaling
  2. CGRP Receptor

MK-0974 (Synonyms: Telcagepant)

Cat. No.: HY-32709 Purity: 98.52% ee.: 98.00%
Data Sheet SDS Handling Instructions

MK-0974 is a highly potent, selective, and orally bioavailable CGRP receptor antagonist with Ki values of 0.77 nM and 1.2 nM for human and rhesus CGRP receptors, respectively, but displays > 1500-fold lower affinity for the canine and rat receptors.

For research use only. We do not sell to patients.
MK-0974 Chemical Structure

MK-0974 Chemical Structure

CAS No. : 781649-09-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO $199 In-stock
2 mg $105 In-stock
5 mg $160 In-stock
10 mg $280 In-stock
50 mg $1200 In-stock
100 mg $2050 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

MK-0974 is a highly potent, selective, and orally bioavailable CGRP receptor antagonist with Ki values of 0.77 nM and 1.2 nM for human and rhesus CGRP receptors, respectively, but displays > 1500-fold lower affinity for the canine and rat receptors.

IC50 & Target

Ki: 0.77 nM (human CGRP), 1.2 nM (rhesus CGRP)

In Vitro

MK-0974 displays affinity (Ki) for the canine and rat receptors, with values of 1204 nM and 1192 nM (n=10), respectively. MK-0974 potently blocks human α-CGRP-stimulated cAMP responses in human CGRP receptor expressing HEK293 cells with an IC50 of 2.2 nM[1]. MK-0974 displays saturable binding to SK-N-MC membranes with a KD of 1.9 nM and Bmax of 479 fmol/mg protein. MK-0974 also displays saturable binding to rhesus cerebellum homogenate with a KDmax of 20 fmol/mg[2].  

In Vivo

MK-0974 (i.v. bolus, 1 mg/kg) demonstrates that the efficacy of this antagonist is time-dependent and correlated with plasma levels[1]. The pharmacokinetics of 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[3].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.7652 mL 8.8258 mL 17.6516 mL
5 mM 0.3530 mL 1.7652 mL 3.5303 mL
10 mM 0.1765 mL 0.8826 mL 1.7652 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

HEK293 cells stably transfected with CLR/RAMP1 are plated in complete growth medium at 85,000 cells/well in 96-well poly-D-lysine-coated plates and cultured for 19 h before assay. Cells are washed with PBS and then incubated with inhibitor in the presence or absence of 50% human serum for 30 min at 37°C and 95% humidity in Cellgro Complete Serum-Free/Low-Protein medium with L-glutamine and 1 g/L bovine serum albumin. Isobutylmethylxanthine is added to the cells at a concentration of 300 μM and incubated for 30 min at 37°C. Human α-CGRP is added to the cells at a concentration of 0.3 nM and allowed to incubate at 37°C for 5 min. After α-CGRP stimulation, the cells are washed with PBS and processed for cAMP determination using the two-stage assay procedure according to the manufacturer's recommended protocol. Dose-response curves are plotted, and IC50 values are determined. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Rhesus monkeys (male and female) weighing between 4 and 10 kg are anesthetized initially with ketamine (0.1 mL/kg i.m.) and then placed in the supine position on a temperature-controlled water circulating blanket and intubated with a 3-mm tracheal tube connected to 1-liter oxygen/1 to 2% isoflurane gas anesthesia. The right saphenous vein is cannulated for intravenous drug delivery, and blood samples are obtained from the left saphenous artery. Four rubber O-rings (8 mm inner diameter) are placed on the ventral side of the forearm without directly being positioned over a visible vessel. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

566.52

Formula

C₂₆H₂₇F₅N₆O₃

CAS No.

781649-09-0

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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MK-0974
Cat. No.:
HY-32709
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