| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
MK-3207 targets the calcitonin gene-related peptide (CGRP) receptor. CGRP is a neuropeptide that plays a key role in the pathophysiology of migraine, including vasodilation and transmission of pain signals. MK-3207 is a highly potent antagonist of the human CGRP receptor with an IC50 of 0.12 nM and a Ki of 0.024 nM. It demonstrates excellent selectivity over human AM1, AM2, CTR, and AMY3 receptors, but shows lower affinity for CGRP receptors from canine and rodent species.
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| ln Vitro |
MK-3207 (0.3, 0.6, 1.1, 2.3, 4.5, 9.0 nM; 30 min) potently inhibits human α-CGRP-stimulated cAMP responses in human CGRP receptor-expressing HEK293 cells[1].
In vitro, MK-3207 demonstrates potent antagonistic activity against the human CGRP receptor with an IC50 of 0.12 nM and a Ki of 0.024 nM. It shows a Ki of 22 pM for the recombinant human receptor and an IC50 of 120 pM in cells expressing the human CGRP receptor. The compound exhibits excellent selectivity over human AM1, AM2, CTR, and AMY3 receptors, but shows lower affinity for canine and rodent CGRP receptors. This species specificity is an important characteristic of the compound. |
| ln Vivo |
MK-3207 (0.3, 0.6, 2.1, 9.1, 21.2, 60.6 µg/kg; i.v.; single) has an EC50 and Emax of roughly 0.8 nM and 81%, respectively, in rhesus monkeys that inhibit CIDV[1].
MK-3207 (10 mg/kg; p.o.; single) indicates a 2–3% CSF/plasma ratio[1]. MK-3207 has been used in trials studying the treatment of migraine and migraine disorders. As an orally active CGRP receptor antagonist, the compound is expected to have efficacy in vivo in blocking CGRP-mediated effects. However, specific in vivo efficacy data from animal models are not detailed in the available sources. The compound's species specificity (lower affinity for rodent CGRP receptors) may limit its use in standard rodent models of migraine. |
| Enzyme Assay |
MK-3207 and 40 pM rat amylin are combined in amylin binding assays, and then 25 μg of CTR/RAMP1 or 25 μg of CTR/RAMP3 membranes are added. The mixture is then incubated for three hours at room temperature in binding buffer (10 mM HEPES, 5 mM MgCl2, and 0.2% bovine serum albumin) in a volume of one milliliter. As the radioligand in calcitonin binding assays, 25 μg of CTR membranes are used with 30 pM 125I-human calcitonin. Filtration through GF/B 96-well filter plates blocked with 0.5% polyethylenimine ends the incubation process. Prism is utilized for data analysis, and the equation Ki=IC50/1 + ([ligand]/KD is used to calculate the Ki value. Saturation binding experiments are used to calculate the KD value for each receptor.
The CGRP receptor binding assay for MK-3207 involves incubating the compound with membrane preparations from cells expressing the human CGRP receptor and a radiolabeled CGRP ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The Ki for displacement of the radioligand is calculated from the competition curve. Functional antagonism is assessed using a cAMP assay, as CGRP receptor activation stimulates adenylyl cyclase and increases cAMP production. Cells expressing the human CGRP receptor are pre-incubated with varying concentrations of MK-3207 and then stimulated with CGRP. The reduction in cAMP is measured using a cAMP assay kit, and IC50 values are calculated. |
| Cell Assay |
MK-3207 exhibits a rhesus monkey receptor affinity (Ki) of 0.024±0.001 nM; n=14) that is comparable to that of humans, but its affinity for the canine and rat receptors is >400-fold lower, at 10 nM and 10±1.2 nM, respectively. With Ki values of 16,500 nM and 156±17 nM, respectively, MK-3207 exhibits high selectivity against the human AM1 (CLR/RAMP2) and AM2 (CLR/RAMP3) receptors. At 1.9±0.58 μM, MK-3207 exhibits a high level of selectivity against human CTR. With a Ki value of 128±25 nM, MK-3207 demonstrates good selectivity against the AMY3 (CTR/RAMP3) receptor as well. However, its Ki value of 0.75±0.13 nM indicates less selectivity against the AMY1 (CTR/RAMP1) receptor. In human CGRP receptor-expressing HEK293 cells, MK-3207 potently inhibits human α-CGRP-stimulated cAMP responses (IC50 value: 0.12±0.02 nM). MK-3207 exhibits a pIC50 of 7.31±0.09, indicating a significantly lower potency for the rat CGRP receptor.
To evaluate the cellular activity of MK-3207, cells expressing the human CGRP receptor are seeded in 96-well plates. Cells are pre-incubated with varying concentrations of MK-3207 and then stimulated with CGRP. The intracellular cAMP levels are measured using a cAMP assay kit. The IC50 for inhibition of CGRP-induced cAMP production is calculated. The compound's selectivity can be assessed by testing against other related receptors, such as AM1, AM2, CTR, and AMY3. The species specificity can be evaluated by testing against CGRP receptors from different species. |
| Animal Protocol |
Dissolved in DMSO; 123.1 μg/kg; i.v.
Adult rhesus monkeys (either sex) with capsaicin-induced dermal vasodilation Specific in vivo animal experiment protocols for MK-3207 are not detailed in the available sources. As an orally active CGRP receptor antagonist, the compound would typically be evaluated in animal models of migraine, such as the nitroglycerin-induced hyperalgesia model or the capsaicin-induced dermal vasodilation model in non-human primates (due to its species specificity). However, specific protocols are not described in the available literature. The compound has been used in clinical trials for migraine. |
| ADME/Pharmacokinetics |
MK-3207 is characterized as being orally active. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 557.59 and a molecular formula of C31H29F2N5O3. It is a small molecule with properties suitable for oral administration. As a compound that has been used in clinical trials, its pharmacokinetic profile has likely been characterized in preclinical species and in humans.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK-3207 are not provided in the available sources. However, the compound has been used in trials studying the treatment of migraine and migraine disorders, indicating that its safety profile has been assessed in clinical studies. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Mk3207 has been used in trials investigating the treatment of migraines and migraine-related diseases.
MK-3207 is an orally active, highly selective, and species-specific CGRP receptor antagonist. It has been used in trials studying the treatment of migraine and migraine disorders. The compound shows potent antagonism of the human CGRP receptor with an IC50 of 0.12 nM and a Ki of 0.024 nM, and shows excellent selectivity over human AM1, AM2, CTR, and AMY3 receptors. It has a molecular formula of C31H29F2N5O3 and a molecular weight of 557.59. |
| Molecular Formula |
C31H29F2N5O3
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| Molecular Weight |
557.590473890305
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| Exact Mass |
557.223
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| Elemental Analysis |
C, 66.78; H, 5.24; F, 6.81; N, 12.56; O, 8.61
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| CAS # |
957118-49-9
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| Related CAS # |
MK-3207 Hydrochloride; 957116-20-0
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| PubChem CID |
25019940
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
812.1±65.0 °C at 760 mmHg
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| Flash Point |
444.9±34.3 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.689
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| LogP |
4.87
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
41
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C1NC2N=CC=CC=2[C@@]21CC1C=CC(=CC=1C2)NC(=O)CN1C(=O)C2(CCCC2)NC[C@H]1C1C=C(F)C=C(F)C=1
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| InChi Key |
AZAANWYREOQRFB-SETSBSEESA-N
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| InChi Code |
InChI=1S/C31H29F2N5O3/c32-21-10-19(11-22(33)13-21)25-16-35-31(7-1-2-8-31)29(41)38(25)17-26(39)36-23-6-5-18-14-30(15-20(18)12-23)24-4-3-9-34-27(24)37-28(30)40/h3-6,9-13,25,35H,1-2,7-8,14-17H2,(H,36,39)(H,34,37,40)/t25-,30+/m0/s1
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| Chemical Name |
2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxospiro[1,3-dihydroindene-2,3'-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide
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| Synonyms |
MK-3207 HCl; MK3207; MK 3207
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.48 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 25.0 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: ≥ 2.5 mg/mL (4.48 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 25.0 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: ≥ 2.5 mg/mL (4.48 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: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7934 mL | 8.9672 mL | 17.9343 mL | |
| 5 mM | 0.3587 mL | 1.7934 mL | 3.5869 mL | |
| 10 mM | 0.1793 mL | 0.8967 mL | 1.7934 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00548353 | Completed | Drug: MK3207 Drug: Comparator: Placebo (unspecified) |
Migraine Disorders | Merck Sharp & Dohme LLC | August 2007 | Phase 1 |
| NCT00712725 | Completed | Drug: MK3207- 2.5 mg Drug: MK3207- 5 mg |
Migraine | Merck Sharp & Dohme LLC | July 2008 | Phase 2 |
Selected CGRP Receptor Antagonists.ACS Med Chem Lett.2010 Jan 12;1(1):24-9. |
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Model predictedvs. observed blood flow by MK-3207 plasma concentration at two capsaicin doses (300 and 1000 μg).Br J Clin Pharmacol.2015 May;79(5):831-7. |
Simulated mean response of inhibition (%) of capsaicin-induced dermal vasodilatation (CIDV) byMK-3207vs.plasma concentrations ofMK-3207.Br J Clin Pharmacol.2015 May;79(5):831-7. |
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