Compounds > mk-0916
Page last updated: 2024-11-11

mk-0916

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

Description

MK-0916: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9797661
CHEMBL ID255259
CHEMBL ID404095
CHEMBL ID3127870
SCHEMBL ID827105
SCHEMBL ID827104
MeSH IDM0590853

Synonyms (20)

Synonym
CHEMBL255259 ,
CHEMBL404095 ,
bdbm50377888
bdbm50377887
unii-bxi2c3derp
bxi2c3derp ,
4h-1,2,4-triazole, 3-(trans-1-(4-chlorophenyl)-3-fluorocyclobutyl)-4,5-dicyclopropyl-
633317-53-0
mk-0916
SCHEMBL827105
SCHEMBL827104
CHEMBL3127870
1365999-86-5
AKOS027325326
3-(trans-(1r,3r)-1-(4-chlorophenyl)-3-fluorocyclobutyl)-4,5-dicyclopropyl-4h-1,2,4-triazole
3-((1s,3s)-1-(4-chlorophenyl)-3-fluorocyclobutyl)-4,5-dicyclopropyl-4h-1,2,4-triazole
Q27274942
3-[1-(4-chlorophenyl)-3-fluorocyclobutyl]-4,5-dicyclopropyl-1,2,4-triazole
PD159988
PD159989

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
"To characterize pharmacokinetic parameters of MK-0916 and its safety and tolerability in lean, healthy male subjects following single and multiple oral doses."( Pharmacokinetic-pharmacodynamic studies of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor MK-0916 in healthy subjects.
Cilissen, C; Crumley, TM; Gottesdiener, KM; Hermanowski-Vosatka, A; Lai, E; Langdon, RB; Ramael, S; Stone, JA; Sun, L; Wagner, JA; Wenning, L; Wright, DH; Yan, K; Yang, AY; Zheng, W, 2013)		0.87
" Plasma and urine drug concentrations were measured for pharmacokinetic analysis."( Pharmacokinetic-pharmacodynamic studies of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor MK-0916 in healthy subjects.
Cilissen, C; Crumley, TM; Gottesdiener, KM; Hermanowski-Vosatka, A; Lai, E; Langdon, RB; Ramael, S; Stone, JA; Sun, L; Wagner, JA; Wenning, L; Wright, DH; Yan, K; Yang, AY; Zheng, W, 2013)		0.61

Dosage Studied

ExcerptRelevanceReference
" In subjects dosed with 6 mg MK-0916 once daily for 14 days, the mean trough plasma concentration was 240 nm and in vivo cortisone-to-cortisol conversion was inhibited by 84%."( Pharmacokinetic-pharmacodynamic studies of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor MK-0916 in healthy subjects.
Cilissen, C; Crumley, TM; Gottesdiener, KM; Hermanowski-Vosatka, A; Lai, E; Langdon, RB; Ramael, S; Stone, JA; Sun, L; Wagner, JA; Wenning, L; Wright, DH; Yan, K; Yang, AY; Zheng, W, 2013)		0.9
" Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS."( Optimization of brain penetrant 11β-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice.
Boyd, S; deSchoolmeester, J; Dossetter, AG; Goldberg, FW; Groombridge, SD; Gutierrez, PM; Kemmitt, PD; Robb, GR; Scott, JS; Sjögren, T; Swales, JG; Turnbull, AV; Wild, MJ, 2014)		0.4
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Corticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)IC50 (µMol)0.01350.00411.066710.0000AID332062
Corticosteroid 11-beta-dehydrogenase isozyme 1Mus musculus (house mouse)IC50 (µMol)0.02700.00200.24103.7600AID332063
Corticosteroid 11-beta-dehydrogenase isozyme 2Mus musculus (house mouse)IC50 (µMol)4.00000.08200.14400.2060AID332065
Corticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)IC50 (µMol)4.00000.00040.63676.4300AID332064
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (11)

Processvia Protein(s)Taxonomy
lung developmentCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
steroid catabolic processCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
response to hypoxiaCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
regulation of blood volume by renal aldosteroneCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
female pregnancyCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
response to xenobiotic stimulusCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
response to foodCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
response to insulinCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
cortisol metabolic processCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
response to glucocorticoidCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
glucocorticoid metabolic processCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (8)

Processvia Protein(s)Taxonomy
protein homodimerization activityCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
7-beta-hydroxysteroid dehydrogenase (NADP+) activityCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
NADP bindingCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
11-beta-hydroxysteroid dehydrogenase (NADP+) activityCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
cortisol dehydrogenase activityCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
steroid bindingCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
steroid bindingCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
NAD bindingCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
11-beta-hydroxysteroid dehydrogenase (NAD+) activityCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membraneCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
membraneCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
endoplasmic reticulum membraneCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
intracellular membrane-bounded organelleCorticosteroid 11-beta-dehydrogenase isozyme 1Homo sapiens (human)
endoplasmic reticulum membraneCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
intracellular membrane-bounded organelleCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
intracellular membrane-bounded organelleCorticosteroid 11-beta-dehydrogenase isozyme 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID332070Plasma concentration in C57B6 mouse at 10 mg/kg2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID1151437Toxicity in type 2 diabetic patient assessed as increase in LDL-cholesterol level at 6 mg/day relative to placebo-control2014Journal of medicinal chemistry, Jun-12, Volume: 57, Issue:11
Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).
AID332065Inhibition of mouse 11-beta-HSD2 by SPA assay2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332073Oral bioavailability in C57B6 mouse at 10 mg/kg2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332063Inhibition of mouse 11-beta-HSD1 by SPA assay2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332072Normalized AUC (0 to 24 hrs) in C57B6 mouse at 10 mg/kg, po2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332064Inhibition of human 11-beta-HSD2 by SPA assay2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332062Inhibition of human 11-beta-HSD1 by SPA assay2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID753389Antihypertensive activity in spontaneously hypertensive rat model assessed as placebo-corrected diastolic BP at 6 mg/day2013Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12
Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension.
AID753388Antihypertensive activity in spontaneously hypertensive rat model assessed as placebo-corrected systolic BP at 6 mg/day2013Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12
Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension.
AID332068Inhibition of 11-beta-HSD1 in mouse pharmacodynamic model assessed as inhibition of [3H]cortisone to [3H]cortisol at 10 mg/kg, po after 4 hrs2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332069Normalized AUC (0 to 24 hrs) in C57B6 mouse at 10 mg/kg, iv2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID1151438Toxicity in type 2 diabetic patient assessed as increase in circulating adrenal androgen at 6 mg/day relative to placebo-control2014Journal of medicinal chemistry, Jun-12, Volume: 57, Issue:11
Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).
AID1151436Reduction in hBA1c in type 2 diabetic patient2014Journal of medicinal chemistry, Jun-12, Volume: 57, Issue:11
Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).
AID332071Half life in C57B6 mouse at 10 mg/kg2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID332067Inhibition of 11-beta-HSD1 in mouse pharmacodynamic model assessed as inhibition of [3H]cortisone to [3H]cortisol at 10 mg/kg, po after 1 hr2008Bioorganic & medicinal chemistry letters, Jun-01, Volume: 18, Issue:11
Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AID1074448Antidiabetic activity in overweight/obese patient with hypertension assessed as reduction of hBA1c level measured at 12 weeks2014Journal of medicinal chemistry, Feb-13, Volume: 57, Issue:3
Optimization of brain penetrant 11β-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (16.67)29.6817
2010's5 (83.33)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.31

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 Index18.31 (24.57)
Research Supply Index2.08 (2.92)
Research Growth Index5.21 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.31)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (16.67%)5.53%
Reviews1 (16.67%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other4 (66.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		3.87211,2,3-triazole
3-(1-adamantyl)-6,7,8,9-tetrahydro-5h-(1,2,4)triazolo(4,3-a)azepine
[no description available]		3.5720
bvt2733
[no description available]		3.1910
dorsomorphin
dorsomorphin: an AMPK inhibitor. dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling.		2.0810aromatic ether;
piperidines;
pyrazolopyrimidine;
pyridines		bone morphogenetic protein receptor antagonist;
EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor
pf 877423
[no description available]		3.1910
pf 915275
[no description available]		3.1910
amg 221
AMG 221: structure in first source		3.1910
ConditionIndicatedRelationship StrengthStudiesTrials
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.0410
Blood Pressure, High
[description not available]		02.0810
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		02.0810
Cardiometabolic Syndrome
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components not only include metabolic dysfunctions of METABOLIC SYNDROME but also HYPERTENSION, and ABDOMINAL OBESITY.		03.4220
Acute Confusional Senile Dementia
[description not available]		03.0110
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)		03.0110
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		03.0110
Glaucoma
An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. (Dictionary of Visual Science, 4th ed)		03.0110
Metabolic Syndrome
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.		03.4220
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.4920
Diabetes Mellitus, Adult-Onset
[description not available]		02.110
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.		02.110