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Purity: ≥98%
MK-0812 (MK0812) is a novel, potent and selective small molecule CCR2 antagonist with potential anti-Inflammatory and immunomodulatory activity. MK0812 caused an increase in the CCR2 ligand CCL2 and a selective decrease in the frequency of peripheral blood monocytes. The therapeutic potential for targeting CXCR2/CXCR1 in human arthritides is highlighted by the significantly greater impact of CXCR2/CXCR1 antagonism in this model of arthritis compared to CCR2 antagonism. In the tissue and synovial fluid of rheumatoid arthritis patients, neutrophils and monocytes are highly prevalent. It was investigated how small molecule chemokine receptor antagonists, like MK-0812, might prevent these cells from migrating in arthritis caused by anti-collagen antibodies.
| Targets |
CCR2
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| ln Vitro |
MK-0812 completely inhibits every MCP-1 mediated response in a concentration-dependent manner, with an IC50 of 3.2 nM. This value is comparable to the potency (IC50 4.5 nM) reported for MK-0812's inhibition of 125I-MCP-1 binding on isolated monocytes. Specifically, the antagonist causes a monocyte forward scatter measurement below unstimulated or basal levels in addition to totally blocking the shape change response to exogenous MCP-1. MK-0812 added to rhesus blood also prevents the shape change of monocytes induced by MCP-1. MK0812 is a powerful and specific small molecule antagonist of CCR2[2].
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| Enzyme Assay |
Human whole blood is drawn into EDTA tubes and used right away—within an hour. Blood (200 µL) is pre-incubated for 30 minutes at room temperature with MK-0812 (0.1% final DMSO concentration) for antagonist treated samples. Next, 4 µL of chemokine or buffer and 20 µL of FITC conjugated anti-CD14 antibody are added to each sample and gently mixed. A 100 µL aliquot of the blood mixture is incubated for 10 minutes at 37°C. It is then promptly put on ice and gently fixed for 1 minute with 250 µL of an ice cold fixative (49 mL PBS, 1.0 mL 4% para-formaldehyde). In order to lyse red blood cells, 1.0 mL of an ice-cold lysis solution containing 0.15 M NH4Cl2, 10 mM sodium bicarbonate, and 1 mM EDTA is added. The mixture is then incubated on ice for 20 minutes. Following the complete lysis of red blood cells, 100 µL of 4% para-formaldehyde is added, and flow cytometry is used to analyze the samples for measurements of forward scatter[1].
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| References |
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| Molecular Formula |
C24H34N3O3F3
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|---|---|
| Molecular Weight |
469.54026
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| Exact Mass |
469.55
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| Elemental Analysis |
C, 61.39; H, 7.30; F, 12.14; N, 8.95; O, 10.22
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| CAS # |
624733-88-6
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| Related CAS # |
MK-0812 Succinate; 851916-42-2
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| Appearance |
Solid powder
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| SMILES |
CC(C)[C@@]1(CC[C@H](C1)N[C@H]2CCOC[C@H]2OC)C(=O)N3CCC4=C(C3)C=C(C=N4)C(F)(F)F.C(CC(=O)O)C(=O)O
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| InChi Key |
MTMDXAIUENDNDL-RJSMDTJLSA-N
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| InChi Code |
InChI=1S/C24H34F3N3O3/c1-15(2)23(7-4-18(11-23)29-20-6-9-33-14-21(20)32-3)22(31)30-8-5-19-16(13-30)10-17(12-28-19)24(25,26)27/h10,12,15,18,20-21,29H,4-9,11,13-14H2,1-3H3/t18-,20+,21-,23+/m1/s1
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| Chemical Name |
[(1S,3R)-3-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone
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| Synonyms |
MK0812; MK 0812; MK-0812
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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: ~100 mg/mL (~213 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 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 (5.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1297 mL | 10.6487 mL | 21.2974 mL | |
| 5 mM | 0.4259 mL | 2.1297 mL | 4.2595 mL | |
| 10 mM | 0.2130 mL | 1.0649 mL | 2.1297 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 |
| NCT00542022 | Completed | Drug: MK0812 / Duration of Treatment: 12 Weeks Drug: Comparator: placebo (unspecified) / Duration of Treatment: 12 Weeks |
Arthritis, Rheumatoid | Merck Sharp & Dohme LLC | June 2004 | Phase 2 |
| NCT00239655 | Terminated | Drug: MK0812 | Relapsing-Remitting Multiple Sclerosis |
Merck Sharp & Dohme LLC | August 2004 | Phase 2 |
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