| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
MK-0557 (MK0557) is a novel, highly selective, orally bioavailable neuropeptide Y5 receptor antagonist with anti-obesity effects. It inhibits neuropeptide Y5 receptor with a Ki of 1.6 nM. MK-0557 has the potential to treat obesity because it may prevent weight gain following weight loss that is brought about by a very-low-calorie diet (VLCD). Strongly orexigenic neuropeptide Y (NPY) is known, and antagonistic effects on NPY Y1 and NPY Y5 receptors (NPYxR) are thought to represent a promising therapeutic target for obesity prevention.
| Targets |
NPY Y5 receptor
Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonistic action on NPY Y1 and NPY Y5 receptors (NPYxR) is thought to represent a promising therapeutic target for obesity prevention. At the human NPY5R, MK-0557 exhibits a Ki=1.3 nM, while its affinities at the rhesus, mouse, and rat NPY5R are comparable. At concentrations of 10 μM, MK-0557 does not exhibit any significant binding to the human, mouse, or NPY1R, NPY2R, or NPY4R[2]. |
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| ln Vitro |
Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonistic action on NPY Y1 and NPY Y5 receptors (NPYxR) is thought to represent a promising therapeutic target for obesity prevention. At the human NPY5R, MK-0557 exhibits a Ki=1.3 nM, while its affinities at the rhesus, mouse, and rat NPY5R are comparable. At concentrations of 10 μM, MK-0557 does not exhibit any significant binding to the human, mouse, or NPY1R, NPY2R, or NPY4R[2].
MK-0557 was reported to have a binding affinity (Ki) of 1.6 nM for the human NPY Y5R in a radioligand binding assay using Sf9 membranes overexpressing a recombinant human chimeric Y5/Y1 receptor. |
| ln Vivo |
MK-0557 significantly inhibits the body-weight gain in diet-induced obese (DIO) mice and counteracts the effects of the NPY5R-selective agonist on hyperphagia and body-weight gain in C57BL/6J mice. Day 35 body-weight gain is reduced by 40% when lean mice fed regular chow are given a medium high-fat diet (4.2 kcal/g) and administered MK-0557 at a dose of 30 mg/kg PO QD[2].
In a 4-day study in diet-induced obese (DIO) rats, MK-0557 (administered at 1.5 mg/kg bid) showed modest anorectic effects (decrease in food intake). The unbound brain concentrations of MK-0557 in this model exceeded the Y5R Ki value by 20-fold. MK-0557 induced a greater decrease in body weight compared to a pair-fed control group, suggesting that the weight loss might not be solely due to reduced food intake. The authors speculated that MK-0557 may have decreased energy expenditure (EE) in the DIO rats, a mechanism previously reported for Y5R antagonists. [1] |
| Animal Protocol |
The anti-obesity effects of MK-0557 were evaluated in a 4-day study using a diet-induced obese (DIO) rat model.
MK-0557 was administered orally at a dose of 1.5 mg/kg twice daily (bid). Food intake and body weight changes were monitored and compared with a vehicle control group and a pair-fed control group. [1] |
| ADME/Pharmacokinetics |
The calculated lipophilicity (clogP) of MK-0557 was 2.0 (as shown in Table 1). The intrinsic clearance (Clint) values of human liver microsomes and mouse liver microsomes formulations were not determined in this study (as shown in Table 1).
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| References |
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| Additional Infomation |
MK0557 has been used in research to treat schizophrenia and paranoid schizophrenia. MK-0557 is a neuropeptide Y5 receptor (Y5R) antagonist that was in human clinical trials for the treatment of obesity. Its clinical development was terminated because the weight loss observed in the Phase II trial was deemed "not clinically significant." In preclinical studies, MK0557 has been shown to reduce food intake and weight gain in obese animal models. [1]
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| Molecular Formula |
C22H19FN4O3
|
|---|---|
| Molecular Weight |
406.4097
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| Exact Mass |
406.144
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| Elemental Analysis |
C, 65.02; H, 4.71; F, 4.67; N, 13.79; O, 11.81
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| CAS # |
328232-95-7
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| Related CAS # |
935765-76-7 (alternate)
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| PubChem CID |
11491176
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| Appearance |
White to off-white solid powder
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| LogP |
3.022
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
669
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=C([H])C([H])=C([H])C([H])=C1N1C([H])=C([H])C(=N1)N([H])C(C1([H])C([H])([H])C([H])([H])C2(C3C([H])=NC([H])=C([H])C=3C(=O)O2)C([H])([H])C1([H])[H])=O
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| InChi Key |
RMYZIRFUCOMQRH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H19FN4O3/c23-17-3-1-2-4-18(17)27-12-8-19(26-27)25-20(28)14-5-9-22(10-6-14)16-13-24-11-7-15(16)21(29)30-22/h1-4,7-8,11-14H,5-6,9-10H2,(H,25,26,28)
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| Chemical Name |
N-[1-(2-fluorophenyl)pyrazol-3-yl]-1'-oxospiro[cyclohexane-4,3'-furo[3,4-c]pyridine]-1-carboxamide
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| Synonyms |
MK-0557; MK 0557; MK0557
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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: ~200 mg/mL (~492.1 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (12.30 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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 | 2.4606 mL | 12.3028 mL | 24.6057 mL | |
| 5 mM | 0.4921 mL | 2.4606 mL | 4.9211 mL | |
| 10 mM | 0.2461 mL | 1.2303 mL | 2.4606 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 |
| NCT00482430 | Completed | Drug: MK0557 Drug: Comparator: Placebo (unspecified) |
Schizophrenia Paranoid Schizophrenia |
Merck Sharp & Dohme LLC | September 2007 | Phase 2 |
| NCT00533598 | Completed | Drug: MK0557 | Obesity | Merck Sharp & Dohme LLC | September 2002 | Phase 2 |
| NCT00092872 | Completed | Drug: MK0557 | Obesity | Merck Sharp & Dohme LLC | November 2003 | Phase 3 |
| NCT00092859 | Completed | Drug: MK0557 | Obesity | Merck Sharp & Dohme LLC | August 2003 | Phase 3 |
| NCT00533481 | Completed | Drug: MK0557 | Obesity | Merck Sharp & Dohme LLC | February 2004 | Phase 2 |
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