Compounds > mk-0557
Page last updated: 2024-11-12

mk-0557

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID11491176
CHEMBL ID595573
CHEMBL ID4591460
SCHEMBL ID742900
SCHEMBL ID742899
SCHEMBL ID13465189
SCHEMBL ID12674643
MeSH IDM0504813

Synonyms (34)

Synonym
935765-76-7
mk 0557
spiro(cyclohexane-1,3'(1'h)-furo(3,4-c)pyridine)-4-carboxamide, n-(1-(2-fluorophenyl)-1h-pyrazol-3-yl)-3'a,6',7',7'a-tetrahydro-1'-oxo-, (1alpha,4beta)-
CHEMBL595573 ,
mk-0557
mk0557
trans-n-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3h),1''-cyclohexane]-4''-carboxamide
bdbm50304300
trans-n-(1-(2-fluorophenyl)-3-pyrazolyl)-3-oxospiro(6-azaisobenzofuran-1(3h),1'-cyclohexane)-4'-carboxamide
spiro(cyclohexane-1,3'(1'h)-furo(3,4-c)pyridine)-4-carboxamide, n-(1-(2-fluorophenyl)-1h-pyrazol-3-yl)-1'-oxo-, trans-
unii-hve36p8422
328232-95-7
hve36p8422 ,
SCHEMBL742900
SCHEMBL742899
SCHEMBL13465189
SCHEMBL12674643
AC-35453
EX-A1270
(1s,4s)-n-(1-(2-fluorophenyl)-1h-pyrazol-3-yl)-1'-oxo-1'h-spiro[cyclohexane-1,3'-furo[3,4-c]pyridine]-4-carboxamide
HY-15411
CS-6367
DB12168
BCP19822
mk-0557;mk 0557
EX-A1636
mk 0557 - bio-x
Q27280118
MS-26961
CHEMBL4591460
n-[1-(2-fluorophenyl)pyrazol-3-yl]-1'-oxospiro[cyclohexane-4,3'-furo[3,4-c]pyridine]-1-carboxamide
(1r,4r)-n-[1-(2-fluorophenyl)-1h-pyrazol-3-yl]-1'-oxo-1'h-spiro[cyclohexane-1,3'-furo[3,4-c]pyridine]-4-carboxamide
EN300-19854531
Z3294900677

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" Optimisation led to the identification of the brain penetrant, orally bioavailable Y5 antagonist 9b which significantly inhibited the food intake induced by a Y5 selective agonist with a minimal effective dose of 30mg/kg po."( Design, synthesis and SAR of a novel series of benzimidazoles as potent NPY Y5 antagonists.
Bentley, J; Biagetti, M; Caberlotto, L; Contini, S; Di Fabio, R; Genski, T; Leslie, CP; Mazzali, A; Pizzi, DA; Sabbatini, FM; Seri, C; Zonzini, L, 2010)		0.36
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Neuropeptide Y receptor type 5Homo sapiens (human)IC50 (µMol)0.00130.00130.33932.7000AID455395; AID538433
Neuropeptide Y receptor type 5Homo sapiens (human)Ki0.00160.00151.66775.0000AID656904
Neuropeptide Y receptor type 5Rattus norvegicus (Norway rat)IC50 (µMol)0.00210.00140.00170.0021AID455405
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (15)

Processvia Protein(s)Taxonomy
positive regulation of acute inflammatory responseNeuropeptide Y receptor type 5Homo sapiens (human)
negative regulation of acute inflammatory response to antigenic stimulusNeuropeptide Y receptor type 5Homo sapiens (human)
outflow tract morphogenesisNeuropeptide Y receptor type 5Homo sapiens (human)
cardiac left ventricle morphogenesisNeuropeptide Y receptor type 5Homo sapiens (human)
neuropeptide signaling pathwayNeuropeptide Y receptor type 5Homo sapiens (human)
negative regulation of glutamate secretionNeuropeptide Y receptor type 5Homo sapiens (human)
negative regulation of synaptic transmission, GABAergicNeuropeptide Y receptor type 5Homo sapiens (human)
eating behaviorNeuropeptide Y receptor type 5Homo sapiens (human)
negative regulation of apoptotic processNeuropeptide Y receptor type 5Homo sapiens (human)
positive regulation of smooth muscle cell proliferationNeuropeptide Y receptor type 5Homo sapiens (human)
generation of ovulation cycle rhythmNeuropeptide Y receptor type 5Homo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeNeuropeptide Y receptor type 5Homo sapiens (human)
synaptic signaling via neuropeptideNeuropeptide Y receptor type 5Homo sapiens (human)
chemical synaptic transmissionNeuropeptide Y receptor type 5Homo sapiens (human)
G protein-coupled receptor signaling pathwayNeuropeptide Y receptor type 5Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
neuropeptide Y receptor activityNeuropeptide Y receptor type 5Homo sapiens (human)
pancreatic polypeptide receptor activityNeuropeptide Y receptor type 5Homo sapiens (human)
peptide YY receptor activityNeuropeptide Y receptor type 5Homo sapiens (human)
neuropeptide bindingNeuropeptide Y receptor type 5Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (4)

Processvia Protein(s)Taxonomy
plasma membraneNeuropeptide Y receptor type 5Homo sapiens (human)
presynapseNeuropeptide Y receptor type 5Homo sapiens (human)
GABA-ergic synapseNeuropeptide Y receptor type 5Homo sapiens (human)
plasma membraneNeuropeptide Y receptor type 5Homo sapiens (human)
neuron projectionNeuropeptide Y receptor type 5Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (23)

Assay IDTitleYearJournalArticle
AID455408Inhibition of [D-Trp34]NPY-induced food intake in Sprague-Dawley rat at 3 mg/kg, po treated 2 hrs before [D-Trp34]NPY challenge2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455414Ex vivo Y5 receptor occupancy in mouse brain at plasma level of 10 to 20 ng/ml2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455395Displacement of [125I]PYY from human recombinant Y5 receptor2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455399Drug level in rat brain at 10 mg/kg, po after 2 hrs2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID656915Ratio of unbound fraction in rat brain at 5 mg/kg bid to Ki for human recombinant NPYY5 receptor expressed in insect Sf9 membranes2012Bioorganic & medicinal chemistry letters, Apr-15, Volume: 22, Issue:8
Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.
AID656904Displacement of [125I]PPY from human recombinant NPYY5 receptor expressed in insect Sf9 membranes2012Bioorganic & medicinal chemistry letters, Apr-15, Volume: 22, Issue:8
Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.
AID656906Intrinsic clearance in rat liver microsomes2012Bioorganic & medicinal chemistry letters, Apr-15, Volume: 22, Issue:8
Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.
AID656914Antiobesity activity in diet-induced obese rat assessed as decrease body weight at 5 mg/kg bid2012Bioorganic & medicinal chemistry letters, Apr-15, Volume: 22, Issue:8
Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.
AID455409Inhibition of [D-Trp34]NPY-induced food intake in Sprague-Dawley rat at 10 mg/kg, po treated 2 hrs before [D-Trp34]NPY challenge2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID656905Intrinsic clearance in human liver microsomes2012Bioorganic & medicinal chemistry letters, Apr-15, Volume: 22, Issue:8
Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.
AID455406Inhibition of [D-Trp34]NPY-induced food intake in Sprague-Dawley rat at 0.3 mg/kg, po treated 2 hrs before [D-Trp34]NPY challenge2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455407Inhibition of [D-Trp34]NPY-induced food intake in Sprague-Dawley rat at 1 mg/kg, po treated 2 hrs before [D-Trp34]NPY challenge2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455410Inhibition of NPY-induced food intake in Sprague-Dawley rat at 10 mg/kg, po treated 2 hrs before [D-Trp34]NPY challenge2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455405Inhibition of rat Y5 receptor2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455400Drug level in rat CSF at 10 mg/kg, po after 2 hrs2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID538433Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay2010Bioorganic & medicinal chemistry letters, Dec-01, Volume: 20, Issue:23
Design, synthesis and SAR of a novel series of benzimidazoles as potent NPY Y5 antagonists.
AID455404Inhibition of [D-Trp34]NPY-induced food intake in Sprague-Dawley rat assessed as minimum effective dose treated po 2 hrs before [D-Trp34]NPY challenge2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455412Ratio of permeability from basolateral to apical side to apical to basolateral side in pig LLC-PK1 cells expressing mouse MDR1a after 3 hrs2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455398Plasma concentration in rat at 10 mg/kg, po after 2 hrs2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455396Clearance in rat hepatocytes2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455411Ratio of permeability from basolateral to apical side to apical to basolateral side in pig LLC-PK1 cells expressing human MDR1 after 3 hrs2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID455397Lipophilicity, log D at pH 7.42009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (8)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's5 (62.50)29.6817
2010's2 (25.00)24.3611
2020's1 (12.50)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 17.02

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index17.02 (24.57)
Research Supply Index2.48 (2.92)
Research Growth Index4.32 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (17.02)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (37.50%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other5 (62.50%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
sibutramine
sibutramine: serotonin and norepinephrine transporter inhibitor; Meridia is tradename for sibutramine hydrochloride		3.4211organochlorine compound;
tertiary amino compound		anti-obesity agent;
serotonin uptake inhibitor
orlistat
Orlistat: A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.. orlistat : A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.		3.4211beta-lactone;
carboxylic ester;
formamides;
L-leucine derivative		anti-obesity agent;
bacterial metabolite;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
leptin
Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.		2.0310
ConditionIndicatedRelationship StrengthStudiesTrials
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.0710
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		04.3311
Obesity
A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).		06.1743
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		04.3311
Weight Reduction
[description not available]		04.3822
Weight Loss
Decrease in existing BODY WEIGHT.		09.3822
Weight Gain
Increase in BODY WEIGHT over existing weight.		02.0310