| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Telcagepant targets the calcitonin gene-related peptide (CGRP) receptor. It is a potent and selective antagonist of the human CGRP receptor with an IC50 of 0.77 nM. It blocks the binding of CGRP to receptors within the central and peripheral nervous system. CGRP is a primary neuropeptide involved in migraine pathophysiology.
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| ln Vitro |
Affinities (Ki) of telcagepant (MK-0974) for canine and rat receptors are 1204 nM and 1192 nM (n=10), respectively. With an IC50 of 2.2 nM, telcagepant (MK-0974) efficiently inhibits the human α-CGRP-stimulated cAMP response in HEK293 cells expressing the human CGRP receptor[1]. Telcagepant (MK-0974) exhibits saturating binding with a Bmax of 479 fmol/mg protein and a KD of 1.9 nM on SK-N-MC membranes. Additionally, tetracagepant (MK-0974) demonstrated saturable binding with a Bmax of 20 fmol/mg and a KD of 1.3 nM to rhesus monkey cerebellum homogenate[2].
In vitro, telcagepant is a highly potent antagonist of the CGRP receptor with an IC50 of 0.77 nM. It selectively blocks CGRP receptor activation. It inhibits CGRP-mediated signaling in cell-based assays. Its high potency and selectivity make it a valuable tool for studying CGRP receptor function in migraine and other pain conditions. |
| ln Vivo |
Time-dependent and plasma level-correlated antagonist effectiveness is demonstrated by telcagepant (MK-0974) (iv bolus, 1 mg/kg) [1]. When administered intravenously at doses of 0.5–10 mg/kg, Telcagepant (MK–0974) in monkeys has linear pharmacokinetics; however, the oral area under the plasma concentration–time curve (AUC) rises to 5–30 mg/kg, which is 15 times more than the dosage ratio [3].
In vivo, telcagepant has been investigated for the treatment of migraine. It is orally bioavailable. It blocks CGRP-mediated vasodilation and pain signaling. Clinical trials have demonstrated its efficacy in the acute treatment of migraine. It has been studied as a potential therapeutic agent for migraine prevention. |
| Enzyme Assay |
In vitro receptor binding assays for telcagepant typically involve competitive radioligand binding using membrane preparations expressing human CGRP receptors. Membranes are incubated with radiolabeled CGRP and varying concentrations of the compound. IC50 values are calculated from displacement curves. Functional activity is assessed by measuring cAMP accumulation or calcium mobilization in response to CGRP stimulation.
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| Cell Assay |
Cell-based assays for telcagepant involve culturing cells expressing recombinant human CGRP receptors (e.g., CHO or HEK-293 cells). Cells are treated with telcagepant at concentrations ranging from 0.01 nM to 1 µM. Receptor antagonism is measured by inhibiting CGRP-stimulated cAMP accumulation or calcium mobilization. Functional selectivity is assessed by comparing responses at different receptor subtypes.
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| Animal Protocol |
In vivo animal experiments for telcagepant typically involve administration to rodent models of migraine or pain via oral gavage or intravenous injection. CGRP-induced vasodilation is measured by laser Doppler flowmetry. Pain behaviors are assessed in models of trigeminal pain. Pharmacokinetic parameters are evaluated by measuring compound levels in blood and brain.
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| ADME/Pharmacokinetics |
Telcagepant (molecular weight ~550-600) is orally bioavailable. It penetrates the blood-brain barrier to reach its central nervous system targets. It is metabolized in the liver and excreted via bile and urine. Detailed pharmacokinetic parameters including absorption, distribution, metabolism, and excretion are available in clinical pharmacology literature.
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| Toxicity/Toxicokinetics |
Telcagepant is generally well-tolerated. Common side effects include nausea, dizziness, and somnolence. It was not approved by the FDA due to hepatotoxicity concerns observed in some clinical trials. Comprehensive toxicological evaluation has been conducted in preclinical and clinical studies. It is a research tool for studying CGRP receptor function.
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| References |
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| Additional Infomation |
Telcagepant has been investigated for the treatment of migraines. It is a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP being a major neuropeptide involved in the pathophysiological process of migraines. CGRP and its receptors are present in areas of the central and peripheral nervous systems crucial for migraine pain transmission. During a migraine attack, CGRP activates these receptors and promotes the transmission of pain impulses. Indications: Migraine with or without aura. Mechanism of Action: Telcagepant blocks the binding of CGRP to receptors in areas of the central and peripheral nervous systems crucial for migraine pain transmission, thereby inhibiting the transmission of pain signals that lead to migraines.
Telcagepant (CAS#: 781649-09-0) is a selective, orally bioavailable CGRP receptor antagonist. It has an IC50 of 0.77 nM. It has been investigated for migraine treatment. It blocks CGRP binding to receptors in the central and peripheral nervous system. It was not approved due to hepatotoxicity concerns. |
| Molecular Formula |
C26H27F5N6O3
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|---|---|
| Molecular Weight |
566.5230
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| Exact Mass |
566.206
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| CAS # |
781649-09-0
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| PubChem CID |
11319053
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.613
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| LogP |
2.59
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
40
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| Complexity |
948
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1C[C@H](C(=O)N(C[C@@H]1C2=C(C(=CC=C2)F)F)CC(F)(F)F)NC(=O)N3CCC(CC3)N4C5=C(NC4=O)N=CC=C5
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| InChi Key |
CGDZXLJGHVKVIE-DNVCBOLYSA-N
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| InChi Code |
InChI=1S/C26H27F5N6O3/c27-18-4-1-3-17(21(18)28)15-6-7-19(23(38)36(13-15)14-26(29,30)31)33-24(39)35-11-8-16(9-12-35)37-20-5-2-10-32-22(20)34-25(37)40/h1-5,10,15-16,19H,6-9,11-14H2,(H,33,39)(H,32,34,40)/t15-,19-/m1/s1
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| Chemical Name |
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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~88.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (5.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (5.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3 mg/mL (5.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.62 mg/mL (4.62 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.62 mg/mL (4.62 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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