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.

Physicochemical Properties

Molecular Formula	C22H19FN4O3
Molecular Weight	406.4097
Exact Mass	406.144
Elemental Analysis	C, 65.02; H, 4.71; F, 4.67; N, 13.79; O, 11.81
CAS #	328232-95-7
Related CAS #	935765-76-7 (alternate)
PubChem CID	11491176
Appearance	White to off-white solid powder
LogP	3.022
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	30
Complexity	669
Defined Atom Stereocenter Count	0
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
InChi Key	RMYZIRFUCOMQRH-UHFFFAOYSA-N
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)
Chemical Name	N-[1-(2-fluorophenyl)pyrazol-3-yl]-1'-oxospiro[cyclohexane-4,3'-furo[3,4-c]pyridine]-1-carboxamide
Synonyms	MK-0557; MK 0557; MK0557
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	NPY Y5 receptor
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].
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].
References	[1]. Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2738-43. [2]. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab. 2006 Oct;4(4):275-82.
Additional Infomation	MK0557 has been investigated for the treatment of Schizophrenia and Paranoid Schizophrenia.

Solubility Data

Solubility (In Vitro)

DMSO: ~200 mg/mL (~492.1 mM) H2O: < 0.1 mg/mL

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.