Compounds > ly2456302
Page last updated: 2024-11-13

ly2456302

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Description

Aticaprant: a kappa opioid receptor antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID44129648
CHEMBL ID1921847
SCHEMBL ID2638855
MeSH IDM000597125

Synonyms (38)

Synonym
1174130-61-0
(s)-4-(4-((2-(3,5-dimethylphenyl)pyrrolidin-1-yl)methyl)phenoxy)-3-fluorobenzamide
jspa0658
CHEMBL1921847 ,
jnj-67953964-aaa
jspa-0658
ly-2456302
cerc-501
bdbm50358171
ly2456302
jnj-67953964
aticaprant
aticaprant [inn]
unii-de4g8x55f5
aticaprant [usan]
de4g8x55f5 ,
benzamide, 4-(4-(((2s)-2-(3,5-dimethylphenyl)-1-pyrrolidinyl)methyl)phenoxy)-3-fluoro-
who 10582
SCHEMBL2638855
DTXSID90151777
jnj67953964
gtpl9194
cerc501
4-[4-[[(2s)-2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide
HY-101718
CS-6653
aticaprant (usan/inn)
D11831
(s)-3-fluoro-4-(4-((2-(3,5-dimethylphenyl)pyrrolidin-1yl)methyl)-phenoxy)benzamide
DB12341
4-[4-[[(2s)-2-(3,5-dimethylphenyl)-1-pyrrolidinyl]methyl]phenoxy]-3-fluorobenzamide
mfcd22572355
EX-A2610
cerc-501; ly-2456302
Q18344482
MS-27322
ly-2456302cerc-501
AC-36176

Research Excerpts

Overview

LY2456302 is a centrally-penetrant, potent, kappa-selective antagonist with pharmacokinetic properties favorable for clinical development and activity in animal models. It demonstrates >30-fold functional selectivity over mu and delta opioid receptors.

ExcerptReferenceRelevance
"LY2456302 is a centrally-penetrant, potent, kappa-selective antagonist with pharmacokinetic properties favorable for clinical development and activity in animal models predictive of efficacy in mood and addictive disorders."( LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders.
Adams, BL; Anderson, WH; Cramer, JW; Crile, RS; Diaz, N; Eberle, EL; Forster, BM; Jimenez, A; Kahl, SD; Knopp, KL; Li, X; McKinzie, DL; McKinzie, JH; Mitch, CH; Pedregal, C; Quimby, SJ; Rorick-Kehn, LM; Sahr, AE; Shaw, DB; Statnick, MA; Witkin, JM; Wong, CJ, 2014)		2.57
"LY2456302 is a high-affinity, selective kappa opioid antagonist that demonstrates >30-fold functional selectivity over mu and delta opioid receptors."( Safety, tolerability, and pharmacokinetic evaluation of single- and multiple-ascending doses of a novel kappa opioid receptor antagonist LY2456302 and drug interaction with ethanol in healthy subjects.
Bell, RL; Dickinson, GL; Gonzales, CR; Lowe, SL; Rorick-Kehn, L; Royalty, J; Stoltz, RR; Tauscher-Wisniewski, S; Weller, M; Witcher, J; Wong, CJ, 2014)		1.33

Pharmacokinetics

ExcerptReferenceRelevance
" LY2456302 displayed rapid oral absorption and a terminal half-life of approximately 30-40 hours."( Safety, tolerability, and pharmacokinetic evaluation of single- and multiple-ascending doses of a novel kappa opioid receptor antagonist LY2456302 and drug interaction with ethanol in healthy subjects.
Bell, RL; Dickinson, GL; Gonzales, CR; Lowe, SL; Rorick-Kehn, L; Royalty, J; Stoltz, RR; Tauscher-Wisniewski, S; Weller, M; Witcher, J; Wong, CJ, 2014)		1.52

Bioavailability

ExcerptReferenceRelevance
" LY2456302 exhibits canonical pharmacokinetic properties that are favorable for clinical development, with rapid absorption (t(max): 1-2 h) and good oral bioavailability (F = 25%)."( LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders.
Adams, BL; Anderson, WH; Cramer, JW; Crile, RS; Diaz, N; Eberle, EL; Forster, BM; Jimenez, A; Kahl, SD; Knopp, KL; Li, X; McKinzie, DL; McKinzie, JH; Mitch, CH; Pedregal, C; Quimby, SJ; Rorick-Kehn, LM; Sahr, AE; Shaw, DB; Statnick, MA; Witkin, JM; Wong, CJ, 2014)		2.76

Dosage Studied

ExcerptRelevanceReference
" On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing."( A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior.
Babalonis, S; Comer, SD; Fraser, H; Jones, JD; Kelsh, D; Lofwall, MR; Marcus, R; Martinez, DM; Martinez, S; Nunes, EV; Paterson, B; Vince, B; Walsh, SL, 2020)		0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Mu-type opioid receptorHomo sapiens (human)Ki0.01960.00000.419710.0000AID631360; AID727334
Delta-type opioid receptorHomo sapiens (human)Ki0.14400.00000.59789.9300AID631361; AID727332
Kappa-type opioid receptorHomo sapiens (human)Ki0.00080.00000.362410.0000AID1191369; AID631359; AID727333
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Mu-type opioid receptorHomo sapiens (human)Kb0.02500.00000.03310.1792AID1454583; AID631365; AID727338
Delta-type opioid receptorHomo sapiens (human)Kb0.07400.00120.10000.5502AID1454582; AID631347; AID727335
Kappa-type opioid receptorHomo sapiens (human)Kb0.08850.00030.05000.2640AID1454581; AID631364; AID727336
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (52)

Processvia Protein(s)Taxonomy
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMu-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
sensory perceptionMu-type opioid receptorHomo sapiens (human)
negative regulation of cell population proliferationMu-type opioid receptorHomo sapiens (human)
sensory perception of painMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
behavioral response to ethanolMu-type opioid receptorHomo sapiens (human)
positive regulation of neurogenesisMu-type opioid receptorHomo sapiens (human)
negative regulation of Wnt protein secretionMu-type opioid receptorHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeMu-type opioid receptorHomo sapiens (human)
calcium ion transmembrane transportMu-type opioid receptorHomo sapiens (human)
cellular response to morphineMu-type opioid receptorHomo sapiens (human)
regulation of cellular response to stressMu-type opioid receptorHomo sapiens (human)
regulation of NMDA receptor activityMu-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayMu-type opioid receptorHomo sapiens (human)
immune responseDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerDelta-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
adult locomotory behaviorDelta-type opioid receptorHomo sapiens (human)
negative regulation of gene expressionDelta-type opioid receptorHomo sapiens (human)
negative regulation of protein-containing complex assemblyDelta-type opioid receptorHomo sapiens (human)
positive regulation of CREB transcription factor activityDelta-type opioid receptorHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylationDelta-type opioid receptorHomo sapiens (human)
response to nicotineDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
eating behaviorDelta-type opioid receptorHomo sapiens (human)
regulation of mitochondrial membrane potentialDelta-type opioid receptorHomo sapiens (human)
regulation of calcium ion transportDelta-type opioid receptorHomo sapiens (human)
cellular response to growth factor stimulusDelta-type opioid receptorHomo sapiens (human)
cellular response to hypoxiaDelta-type opioid receptorHomo sapiens (human)
cellular response to toxic substanceDelta-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayDelta-type opioid receptorHomo sapiens (human)
immune responseKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
chemical synaptic transmissionKappa-type opioid receptorHomo sapiens (human)
sensory perceptionKappa-type opioid receptorHomo sapiens (human)
locomotory behaviorKappa-type opioid receptorHomo sapiens (human)
sensory perception of painKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
response to insulinKappa-type opioid receptorHomo sapiens (human)
positive regulation of dopamine secretionKappa-type opioid receptorHomo sapiens (human)
negative regulation of luteinizing hormone secretionKappa-type opioid receptorHomo sapiens (human)
response to nicotineKappa-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
maternal behaviorKappa-type opioid receptorHomo sapiens (human)
eating behaviorKappa-type opioid receptorHomo sapiens (human)
response to estrogenKappa-type opioid receptorHomo sapiens (human)
estrous cycleKappa-type opioid receptorHomo sapiens (human)
response to ethanolKappa-type opioid receptorHomo sapiens (human)
regulation of saliva secretionKappa-type opioid receptorHomo sapiens (human)
behavioral response to cocaineKappa-type opioid receptorHomo sapiens (human)
sensory perception of temperature stimulusKappa-type opioid receptorHomo sapiens (human)
defense response to virusKappa-type opioid receptorHomo sapiens (human)
cellular response to lipopolysaccharideKappa-type opioid receptorHomo sapiens (human)
cellular response to glucose stimulusKappa-type opioid receptorHomo sapiens (human)
positive regulation of p38MAPK cascadeKappa-type opioid receptorHomo sapiens (human)
positive regulation of potassium ion transmembrane transportKappa-type opioid receptorHomo sapiens (human)
response to acrylamideKappa-type opioid receptorHomo sapiens (human)
positive regulation of eating behaviorKappa-type opioid receptorHomo sapiens (human)
conditioned place preferenceKappa-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayKappa-type opioid receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (12)

Processvia Protein(s)Taxonomy
G-protein alpha-subunit bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled receptor activityMu-type opioid receptorHomo sapiens (human)
beta-endorphin receptor activityMu-type opioid receptorHomo sapiens (human)
voltage-gated calcium channel activityMu-type opioid receptorHomo sapiens (human)
protein bindingMu-type opioid receptorHomo sapiens (human)
morphine receptor activityMu-type opioid receptorHomo sapiens (human)
G-protein beta-subunit bindingMu-type opioid receptorHomo sapiens (human)
neuropeptide bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityDelta-type opioid receptorHomo sapiens (human)
protein bindingDelta-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled enkephalin receptor activityDelta-type opioid receptorHomo sapiens (human)
neuropeptide bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityKappa-type opioid receptorHomo sapiens (human)
protein bindingKappa-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingKappa-type opioid receptorHomo sapiens (human)
dynorphin receptor activityKappa-type opioid receptorHomo sapiens (human)
neuropeptide bindingKappa-type opioid receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (23)

Processvia Protein(s)Taxonomy
endosomeMu-type opioid receptorHomo sapiens (human)
endoplasmic reticulumMu-type opioid receptorHomo sapiens (human)
Golgi apparatusMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
axonMu-type opioid receptorHomo sapiens (human)
dendriteMu-type opioid receptorHomo sapiens (human)
perikaryonMu-type opioid receptorHomo sapiens (human)
synapseMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
neuron projectionMu-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneDelta-type opioid receptorHomo sapiens (human)
dendrite membraneDelta-type opioid receptorHomo sapiens (human)
presynaptic membraneDelta-type opioid receptorHomo sapiens (human)
axon terminusDelta-type opioid receptorHomo sapiens (human)
spine apparatusDelta-type opioid receptorHomo sapiens (human)
postsynaptic density membraneDelta-type opioid receptorHomo sapiens (human)
neuronal dense core vesicleDelta-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
neuron projectionDelta-type opioid receptorHomo sapiens (human)
nucleoplasmKappa-type opioid receptorHomo sapiens (human)
mitochondrionKappa-type opioid receptorHomo sapiens (human)
cytosolKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
membraneKappa-type opioid receptorHomo sapiens (human)
sarcoplasmic reticulumKappa-type opioid receptorHomo sapiens (human)
T-tubuleKappa-type opioid receptorHomo sapiens (human)
dendriteKappa-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneKappa-type opioid receptorHomo sapiens (human)
presynaptic membraneKappa-type opioid receptorHomo sapiens (human)
perikaryonKappa-type opioid receptorHomo sapiens (human)
axon terminusKappa-type opioid receptorHomo sapiens (human)
postsynaptic membraneKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
neuron projectionKappa-type opioid receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (58)

Assay IDTitleYearJournalArticle
AID1401137Tmax in rat at 1 mg/kg, iv2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID631391Selectivity ratio of Kb for human opioid delta receptor expressed in HEK293 cells to Kb for human opioid kappa receptor expressed in CHO cells2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID727331In vivo receptor occupancy at DOR in po dosed Harlan Sprague-Dawley rat brain after 5.5 hrs by LC/MS/MS analysis2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID631360Displacement of [3H]diprenorphine from human opioid mu receptor expressed in CHO cells after 120 mins by scintillation counting2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID631394Agonist activity at human opioid delta receptor expressed in HEK293 cells assessed as stimulation of [35S]-GTPgammaS binding at 10 uM2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1454584Selectivity ratio of Kb for human mu opioid receptor to Kb for human kappa opioid receptor
AID1139370Clearance in rat at 1 mg/kg, iv2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID631392Agonist activity at human opioid kappa receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding at 10 uM2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID727338Antagonist activity at human cloned MOR assessed as inhibition of DAMGO-stimulated [35S]GTPgammaS binding after 4 hrs by scintillation counting analysis2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID1480733Oral bioavailability in rat at 10 mg/kg by LC-MS/MS analysis2017European journal of medicinal chemistry, Apr-21, Volume: 130Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists.
AID1480734Tmax in rat at 1 or 10 mg/kg, iv or po by LC-MS/MS analysis2017European journal of medicinal chemistry, Apr-21, Volume: 130Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists.
AID631361Displacement of [3H]diprenorphine from human opioid delta receptor expressed in HEK293 cells after 120 mins by scintillation counting2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1139374Half life in rat at 10 mg/kg, po2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID727334Binding affinity to human cloned MOR in presence of Na+/GDP2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID631347Antagonist activity at human opioid delta receptor expressed in HEK293 cells assessed as inhibition of DPDPE-induced [35S]GTP-gamma-S binding after 4 hrs by scintillation counting2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1401136Cmax in rat at 1 mg/kg, iv2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID1139368Tmax in rat at 1 mg/kg, iv2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1401141Cmax in rat at 10 mg/kg, po2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID727336Antagonist activity at human cloned KOR assessed as inhibition of U69593-stimulated [35S]GTPgammaS binding after 4 hrs by scintillation counting analysis2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID727333Binding affinity to human cloned KOR in presence of Na+/GDP2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID1139371AUC in rat at 10 mg/kg, po2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1401139Clearance in rat at 1 mg/kg, iv2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID1139367Cmax in rat at 1 mg/kg, iv2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1139377Selectivity ratio for OPRK (unknown origin) to OPRM (unknown origin)2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1401145Analgesic activity in po dosed rat assessed as reversal of U-69593-induced pain response2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID1139366AUC in rat at 1 mg/kg, iv2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1454581Antagonist activity at human kappa-opioid receptor expressed in CHO cell membranes assessed as inhibition of U69593 agonist-induced [35S]GTPgammaS binding after 4 hrs by scintillation counting method
AID631363Selectivity ratio of Ki for human opioid delta receptor expressed in HEK293 cells to Ki for human opioid kappa receptor expressed in CHO cells2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1401143Half life in rat at 10 mg/kg, po2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID1191369Antagonist activity at kappa opioid receptor (unknown origin)2015European journal of medicinal chemistry, Jan-27, Volume: 90Novel fluoroalkyl derivatives of selective kappa opioid receptor antagonist JDTic: Design, synthesis, pharmacology and molecular modeling studies.
AID1401138Half life in rat at 1 mg/kg, iv2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID1139373Tmax in rat at 10 mg/kg, po2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID631393Agonist activity at human opioid mu receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding at 10 uM2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID631359Displacement of [3H]diprenorphine from human opioid kappa receptor expressed in CHO cells after 120 mins by scintillation counting2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1454585Selectivity ratio of Kb for human delta opioid receptor to Kb for human kappa opioid receptor
AID1480735Half life in rat at 1 or 10 mg/kg, iv or po by LC-MS/MS analysis2017European journal of medicinal chemistry, Apr-21, Volume: 130Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists.
AID727330In vivo receptor occupancy at MOR in po dosed Harlan Sprague-Dawley rat brain after 5.5 hrs by LC/MS/MS analysis2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID1139375Oral bioavailability in rat at 10 mg/kg2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1401144Oral bioavailability in rat at 10 mg/kg2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID1191371Selectivity ratio of Ki for delta opioid receptor (unknown origin) to Ki for kappa opioid receptor (unknown origin)2015European journal of medicinal chemistry, Jan-27, Volume: 90Novel fluoroalkyl derivatives of selective kappa opioid receptor antagonist JDTic: Design, synthesis, pharmacology and molecular modeling studies.
AID1401135AUC in rat at 1 mg/kg, iv2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID631348Selectivity ratio of Kb for human opioid mu receptor expressed in CHO cells to Kb for human opioid kappa receptor expressed in CHO cells2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1139369Half life in rat at 1 mg/kg, iv2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1401140AUC in rat at 10 mg/kg, po2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID631364Antagonist activity at human opioid kappa receptor expressed in CHO cells assessed as inhibition of U69593-induced [35S]GTP-gamma-S binding after 4 hrs by scintillation counting2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID631365Antagonist activity at human opioid mu receptor expressed in CHO cells assessed as inhibition of DAMGO-induced [35S]GTP-gamma-S binding after 4 hrs by scintillation counting2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID631362Selectivity ratio of Ki for human opioid mu receptor expressed in CHO cells to Ki for human opioid kappa receptor expressed in CHO cells2011Journal of medicinal chemistry, Dec-08, Volume: 54, Issue:23
Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer.
AID1454583Antagonist activity at human mu-opioid receptor expressed in CHO cell membranes assessed as inhibition of DAMGO agonist-induced [35S]GTPgammaS binding after 4 hrs by scintillation counting method
AID1139372Cmax in rat at 10 mg/kg, po2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID1191370Selectivity ratio of Ki for mu opioid receptor (unknown origin) to Ki for kappa opioid receptor (unknown origin)2015European journal of medicinal chemistry, Jan-27, Volume: 90Novel fluoroalkyl derivatives of selective kappa opioid receptor antagonist JDTic: Design, synthesis, pharmacology and molecular modeling studies.
AID1139376Analgesic activity in po dosed rat assessed as inhibition of formalin response2014Bioorganic & medicinal chemistry letters, May-01, Volume: 24, Issue:9
Antagonists of the kappa opioid receptor.
AID727335Antagonist activity at human cloned DOR assessed as inhibition of DPDPE-stimulated [35S]GTPgammaS binding after 4 hrs by scintillation counting analysis2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID1454582Antagonist activity at human delta-opioid receptor expressed in HEK293 cell membranes assessed as inhibition of DPDPE agonist-induced [35S]GTPgammaS binding after 2 hrs by scintillation counting method
AID1401142Tmax in rat at 10 mg/kg, po2017European journal of medicinal chemistry, Dec-01, Volume: 141Selective kappa opioid antagonists for treatment of addiction, are we there yet?
AID727332Binding affinity to human cloned DOR in presence of Na+/GDP2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development of κ opioid receptor antagonists.
AID1346329Human kappa receptor (Opioid receptors)2014Neuropharmacology, Feb, Volume: 77LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders.
AID1346361Human delta receptor (Opioid receptors)2014Neuropharmacology, Feb, Volume: 77LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders.
AID1346364Human mu receptor (Opioid receptors)2014Neuropharmacology, Feb, Volume: 77LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (21)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's15 (71.43)24.3611
2020's6 (28.57)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 16.47

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 Index16.47 (24.57)
Research Supply Index3.22 (2.92)
Research Growth Index4.51 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (16.47)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (14.29%)5.53%
Reviews4 (19.05%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other14 (66.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide: cyclic somatostatin octapeptide analog with high affinity & selectivity toward mu opioid receptors		2.2510
fentanyl
Fentanyl: A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078). fentanyl : A monocarboxylic acid amide resulting from the formal condensation of the aryl amino group of N-phenyl-1-(2-phenylethyl)piperidin-4-amine with propanoic acid.		3.4811anilide;
monocarboxylic acid amide;
piperidines		adjuvant;
anaesthesia adjuvant;
anaesthetic;
intravenous anaesthetic;
mu-opioid receptor agonist;
opioid analgesic
corticosterone
[no description available]		2.171011beta-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(4) steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone		human metabolite;
mouse metabolite
nicotine
(S)-nicotine : A 3-(1-methylpyrrolidin-2-yl)pyridine in which the chiral centre has S-configuration. The naturally occurring and most active enantiomer of nicotine, isolated from Nicotiana tabacum.		7.57203-(1-methylpyrrolidin-2-yl)pyridineanxiolytic drug;
biomarker;
immunomodulator;
mitogen;
neurotoxin;
nicotinic acetylcholine receptor agonist;
peripheral nervous system drug;
phytogenic insecticide;
plant metabolite;
psychotropic drug;
teratogenic agent;
xenobiotic
enkephalin, d-penicillamine (2,5)-
Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.. DPDPE : A heterodetic cyclic peptide that is a cyclic enkephalin analogue, having D-penicillaminyl residues located at positions 2 and 5, which form the heterocycle via a disulfide bond.		2.2510heterodetic cyclic peptidedelta-opioid receptor agonist
buprenorphine
Buprenorphine: A derivative of the opioid alkaloid THEBAINE that is a more potent and longer lasting analgesic than MORPHINE. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use.. buprenorphine : A morphinane alkaloid that is 7,8-dihydromorphine 6-O-methyl ether in which positions 6 and 14 are joined by a -CH2CH2- bridge, one of the hydrogens of the N-methyl group is substituted by cyclopropyl, and a hydrogen at position 7 is substituted by a 2-hydroxy-3,3-dimethylbutan-2-yl group. It is highly effective for the treatment of opioid use disorder and is also increasingly being used in the treatment of chronic pain.		3.2510morphinane alkaloiddelta-opioid receptor antagonist;
kappa-opioid receptor antagonist;
mu-opioid receptor agonist;
opioid analgesic
u-50488
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer: A non-peptide, kappa-opioid receptor agonist which has also been found to stimulate the release of adrenocorticotropin (ADRENOCORTICOTROPIC HORMONE) via the release of hypothalamic arginine vasopressin (ARGININE VASOPRESSIN) and CORTICOTROPIN-RELEASING HORMONE. (From J Pharmacol Exp Ther 1997;280(1):416-21). U50488 : A monocarboxylic acid amide obtained by formal condensation between the carboxy group of 3,4-dichlorophenylacetic acid and the secondary amino group of (1R,2R)-N-methyl-2-(pyrrolidin-1-yl)cyclohexanamine		2.2110dichlorobenzene;
monocarboxylic acid amide;
N-alkylpyrrolidine		analgesic;
antitussive;
calcium channel blocker;
diuretic;
kappa-opioid receptor agonist
4-[[(4-methylphenyl)sulfonylamino]methyl]-N-[2-[(phenylmethyl)-propan-2-ylamino]ethyl]benzamide
[no description available]		3.1910sulfonamide
morphine
Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.		3.4811morphinane alkaloid;
organic heteropentacyclic compound;
tertiary amino compound		anaesthetic;
drug allergen;
environmental contaminant;
geroprotector;
mu-opioid receptor agonist;
opioid analgesic;
plant metabolite;
vasodilator agent;
xenobiotic
naltrexone
Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.. naltrexone : An organic heteropentacyclic compound that is naloxone substituted in which the allyl group attached to the nitrogen is replaced by a cyclopropylmethyl group. A mu-opioid receptor antagonist, it is used to treat alcohol dependence.		4.2131cyclopropanes;
morphinane-like compound;
organic heteropentacyclic compound		antidote to opioid poisoning;
central nervous system depressant;
environmental contaminant;
mu-opioid receptor antagonist;
xenobiotic
norbinaltorphimine
norbinaltorphimine: kappa opiate receptor antagonist; structure given in first source		3.8730isoquinolines
naltrindole
naltrindole: delta opioid receptor antagonist		2.2510isoquinolines
gr 103545
[no description available]		2.0610
3,4-dichloro-n-methyl-n-(2-(1-pyrrolidinyl)cyclohexyl)-benzeneacetamide, (trans)-(-)-isomer
[no description available]		2.1110acetamides
oxadiazoles
Oxadiazoles: Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.		2.2510
dynorphins
Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.		3.2310
piperidines
Piperidines: A family of hexahydropyridines.		2.6320
cj 15,208
[no description available]		4.1320
pf-04455242
2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine: has antidepressant activity; structure in first source		4.4530
4-[[(4-ethylphenyl)sulfonylamino]methyl]-N-[2-[(phenylmethyl)-propan-2-ylamino]ethyl]benzamide
[no description available]		3.1910sulfonamide
LSM-2536
[no description available]		3.1910piperazines
ConditionIndicatedRelationship StrengthStudiesTrials
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		05.3160
Depression
Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders.		06.0650
Chemical Dependence
[description not available]		03.0110
Anxiety
Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.		15.9840
Substance-Related Disorders
Disorders related to substance use or abuse.		03.0110
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)		02.1510
Addiction, Opioid
[description not available]		03.0610
Ache
[description not available]		03.0610
Opioid-Related Disorders
Disorders related to or resulting from abuse or misuse of OPIOIDS.		03.0610
Pain
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.		03.0610
Affective Disorders
[description not available]		04.5511
Anhedonia
Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many PSYCHOTIC DISORDERS (e.g., DEPRESSIVE DISORDER, MAJOR; and SCHIZOPHRENIA).		04.5511
Anxiety Neuroses
[description not available]		04.5511
Anxiety Disorders
Persistent and disabling ANXIETY.		04.5511
Mood Disorders
Those disorders that have a disturbance in mood as their predominant feature.		04.5511
Chronic Illness
[description not available]		02.2510
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		02.2510
Refractory Depression
[description not available]		02.2510
Depressive Disorder, Treatment-Resistant
Failure to respond to two or more trials of antidepressant monotherapy or failure to respond to four or more trials of different antidepressant therapies. (Campbell's Psychiatric Dictionary, 9th ed.)		14.2510
Cocaine Abuse
[description not available]		02.1710
Itching
[description not available]		02.1710
Pruritus
An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.		02.1710
Cocaine-Related Disorders
Disorders related or resulting from use of cocaine.		02.1710
Alcohol Abuse
[description not available]		02.1710
Drug Withdrawal Symptoms
[description not available]		02.8630
Alcoholism
A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)		02.1710
Substance Withdrawal Syndrome
Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.		02.8630
Nicotine Addiction
[description not available]		02.5720
Tobacco Use Disorder
Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included.		14.5720
Smoking Cessation
Discontinuing the habit of SMOKING.		02.2510
Allodynia
[description not available]		02.5720
Acute Post-operative Pain
[description not available]		02.2510
Pain, Postoperative
Pain during the period after surgery.		02.2510
Alcohol Drinking
Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking.		03.4811
Constricted Pupil
[description not available]		03.4811
Miosis
Pupillary constriction. This may result from congenital absence of the dilatator pupillary muscle, defective sympathetic innervation, or irritation of the CONJUNCTIVA or CORNEA.		03.4811
Mydriasis
Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in ADIE SYNDROME.		03.4811
Depression, Involutional
Form of depression in those MIDDLE AGE with feelings of ANXIETY.		03.0410
Depressive Disorder, Major
Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5)		15.0410