| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
MC4R (melanocortin receptor 4).
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|---|---|
| ln Vitro |
MK-0493 is a potent, orally active, and selective MC4R agonist that significantly reduces food intake. It dose-dependently increases electrically evoked increases in intracavernosal pressure (ICP). The compound has demonstrated significant reductions in energy intake. However, clinical studies have shown that potent and selective agonism of MC4R with MK-0493 did not induce weight loss in obese human subjects, with energy intake predicting lack of weight loss efficacy.
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| ln Vivo |
Electrically induced increases in ICP are dose-dependently increased by MK-0493 [2]. MK-0493 has demonstrated strong weight loss efficacy following oral treatment in preclinical animal models, suggesting that the medication can get to the hypothalamus, where it is intended to work [3].
MK-0493 promotes robust weight loss activity following oral administration in preclinical animal models. It dose-dependently increases electrically evoked increases in ICP. The compound can access the target site in the hypothalamus, suggesting good central nervous system penetration. Despite robust preclinical efficacy, clinical studies showed that MK-0493 did not induce weight loss in obese human subjects, with energy intake predicting lack of weight loss efficacy. |
| Enzyme Assay |
The in vitro receptor binding assay for MC4R agonism uses membrane preparations from cells expressing recombinant human MC4R. MK-0493 is incubated with the receptor preparation and a radiolabeled MC4R ligand (e.g., [125I]NDP-α-MSH) at varying concentrations (typically 0.01 nM to 100 µM). After incubation, bound and free radioactivity are separated by filtration. The Ki or IC50 is calculated from competition binding curves. For functional activity, cAMP accumulation assays are performed in cells expressing MC4R to measure agonist activity. EC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular assays are performed using cells expressing recombinant human MC4R (e.g., HEK293 cells). Cells are treated with MK-0493 at concentrations ranging from 0.01 nM to 100 µM for 30-60 minutes. Intracellular cAMP levels are measured using a competitive immunoassay (e.g., ELISA or HTRF). The EC50 for cAMP accumulation is calculated from dose-response curves. Selectivity is assessed by profiling against other melanocortin receptors (MC1R, MC2R, MC3R, MC5R). Receptor internalization and β-arrestin recruitment assays can also be performed to characterize the compound's signaling profile.
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| Animal Protocol |
In vivo efficacy is evaluated in rodent models of obesity. Mice or rats are administered MK-0493 orally at various doses (e.g., 0.1-10 mg/kg) on a scheduled basis. Food intake is measured daily, and body weight is monitored over the course of the study (typically 7-28 days). Energy expenditure is assessed by indirect calorimetry. For ICP measurements, the compound is administered and electrically evoked increases in ICP are measured as a pharmacodynamic endpoint. Brain penetration is confirmed by measuring drug levels in brain tissue.
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| ADME/Pharmacokinetics |
MK-0493 has a molecular weight of 546.09 g/mol and molecular formula C30H38ClF2N3O2. It is orally bioavailable. The compound is soluble in DMSO (~100 mg/mL). Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and brain penetration have been characterized in preclinical studies. The compound is supplied as a free base form and should be stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for MK-0493. As a research compound and clinical candidate, it has undergone preclinical toxicology assessments including genotoxicity, cardiac safety (hERG channel inhibition), and repeated-dose toxicity studies in rodents and non-rodents. The compound did not induce weight loss in obese human subjects in clinical studies. It is for research use only and not for human therapeutic use outside of clinical trials.
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| References |
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| Additional Infomation |
MK-0493 is a research-grade MC4R agonist that was in clinical development for obesity but did not show efficacy in human trials. It is not approved for clinical use. The compound is also known as MK-0493 free base. It dose-dependently increases electrically evoked increases in ICP and reduces food intake in preclinical models. MK-0493 is supplied as a solid with high purity and should be stored desiccated at -20°C.
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| Molecular Formula |
C30H38CLF2N3O2
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|---|---|
| Molecular Weight |
546.091434001923
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| Exact Mass |
545.262
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| CAS # |
455956-93-1
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| Related CAS # |
455956-93-1;455957-71-8 (HCl);
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| PubChem CID |
11642422
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| Appearance |
White to light yellow solid powder
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
38
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| Complexity |
831
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@@H](C1=C(C=CC(=C1)Cl)C2CCN(CC2)C(=O)[C@@H]3CN(C[C@H]3C4=C(C=C(C=C4)F)F)C(C)(C)C)NC(=O)C
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| InChi Key |
ZCWVNCMFYHPHCX-RHLLTPQKSA-N
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| InChi Code |
InChI=1S/C30H38ClF2N3O2/c1-18(34-19(2)37)25-14-21(31)6-8-23(25)20-10-12-35(13-11-20)29(38)27-17-36(30(3,4)5)16-26(27)24-9-7-22(32)15-28(24)33/h6-9,14-15,18,20,26-27H,10-13,16-17H2,1-5H3,(H,34,37)/t18-,26-,27+/m0/s1
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| Chemical Name |
N-[(1S)-1-[2-[1-[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonyl]piperidin-4-yl]-5-chlorophenyl]ethyl]acetamide
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| Synonyms |
MK-0493; MK 0493; MK0493
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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 (~183.12 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8312 mL | 9.1560 mL | 18.3120 mL | |
| 5 mM | 0.3662 mL | 1.8312 mL | 3.6624 mL | |
| 10 mM | 0.1831 mL | 0.9156 mL | 1.8312 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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