Page last updated: 2024-12-07

kelatorphan

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

Description

kelatorphan: inhibitor of enkephalin metabolism; structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID123982
CHEMBL ID85320
SCHEMBL ID7384459
MeSH IDM0125693

Synonyms (23)

Synonym
CHEMBL85320
n-[(2r)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]-l-alanine
KEL ,
l-alanine, n-(4-(hydroxyamino)-1,4-dioxo-2-(phenylmethyl)butyl)-, (r)-
(3-(n-hydroxy)carboxamido-2-benzylpropanoyl)alanine
kelatorphan
DB08040
(2s)-2-[[(2r)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]amino]propanoic acid
92175-57-0
bdbm92500
46bbw2u5d6 ,
unii-46bbw2u5d6
3B7U
l-alanine, n-((2r)-4-(hydroxyamino)-1,4-dioxo-2-(phenylmethyl)butyl)-
SCHEMBL7384459
HY-10827
CS-0002846
DTXSID90238911
Q6385498
((r)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl)-l-alanine
MS-24208
gtpl11656
AKOS040741909

Research Excerpts

Treatment

ExcerptReferenceRelevance
"Co-treatment with kelatorphan stabilizes putative endogenous opioid peptide agonists released by naloxone in GM1-treated mice, so that analgesia is evoked rather than hyperalgesia."( Naloxone rapidly evokes endogenous kappa opioid receptor-mediated hyperalgesia in naïve mice pretreated briefly with GM1 ganglioside or in chronic morphine-dependent mice.
Crain, SM; Shen, KF, 2007
)
0.66

Bioavailability

ExcerptReferenceRelevance
"Prodrugs of phosphinic dual inhibitors of the enkephalin degrading enzymes, neutral endopeptidase (NEP) and aminopeptidase N (APN), corresponding to the formula H(3)N(+)CH(R(1))P(O)(OR)CH(2)CH(CH(2)Bip)CONHCH(CH(3))COOCH(2)Ph, with R(1) = CH(3) or Ph and R being a benzyl ester, a S-acyl-2-thioethyl derivative, or an acyloxyalkyl group, were synthesized to improve the poor central bioavailability of their precursors."( Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs.
Chen, H; Fournié-Zaluski, MC; Noble, F; Roques, BP, 2001
)
0.31

Dosage Studied

ExcerptRelevanceReference
" Kelatorphan (20 microM) produced a 7-fold shift to the left of the Met-enkephalin dose-response curve."( Potentiation of enkephalin action by peptidase inhibitors in rat locus ceruleus in vitro.
Christie, MJ; North, RA; Roques, BP; Williams, JT, 1987
)
1.18
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (8)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ThermolysinBacillus thermoproteolyticusIC50 (µMol)0.00300.00301.93259.5000AID213074
NeprilysinRattus norvegicus (Norway rat)Ki0.00170.00170.01520.0400AID67357
NeprilysinOryctolagus cuniculus (rabbit)IC50 (µMol)0.00360.00040.66118.2000AID147212; AID147213; AID147516
NeprilysinHomo sapiens (human)Ki0.00170.00150.00440.0090AID147396
Leukotriene A-4 hydrolaseHomo sapiens (human)IC50 (µMol)0.00500.00051.28547.6500AID99747
EEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)Ki0.19500.00120.09810.1950AID1799789
Aminopeptidase NHomo sapiens (human)Ki7.00000.00081.956910.0000AID38380
Aminopeptidase NSus scrofa (pig)Ki0.00380.00052.29697.8000AID35687
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (38)

Processvia Protein(s)Taxonomy
kidney developmentNeprilysinHomo sapiens (human)
placenta developmentNeprilysinHomo sapiens (human)
proteolysisNeprilysinHomo sapiens (human)
peptide metabolic processNeprilysinHomo sapiens (human)
learning or memoryNeprilysinHomo sapiens (human)
substance P catabolic processNeprilysinHomo sapiens (human)
bradykinin catabolic processNeprilysinHomo sapiens (human)
sensory perception of painNeprilysinHomo sapiens (human)
protein catabolic processNeprilysinHomo sapiens (human)
lung developmentNeprilysinHomo sapiens (human)
hormone catabolic processNeprilysinHomo sapiens (human)
response to estrogenNeprilysinHomo sapiens (human)
creatinine metabolic processNeprilysinHomo sapiens (human)
amyloid-beta metabolic processNeprilysinHomo sapiens (human)
positive regulation of neurogenesisNeprilysinHomo sapiens (human)
neuropeptide processingNeprilysinHomo sapiens (human)
cellular response to cytokine stimulusNeprilysinHomo sapiens (human)
cellular response to UV-ANeprilysinHomo sapiens (human)
cellular response to UV-BNeprilysinHomo sapiens (human)
replicative senescenceNeprilysinHomo sapiens (human)
amyloid-beta clearanceNeprilysinHomo sapiens (human)
amyloid-beta clearance by cellular catabolic processNeprilysinHomo sapiens (human)
positive regulation of long-term synaptic potentiationNeprilysinHomo sapiens (human)
protein processingNeprilysinHomo sapiens (human)
proteolysisLeukotriene A-4 hydrolaseHomo sapiens (human)
lipid metabolic processLeukotriene A-4 hydrolaseHomo sapiens (human)
response to zinc ionLeukotriene A-4 hydrolaseHomo sapiens (human)
leukotriene biosynthetic processLeukotriene A-4 hydrolaseHomo sapiens (human)
protein metabolic processLeukotriene A-4 hydrolaseHomo sapiens (human)
peptide catabolic processLeukotriene A-4 hydrolaseHomo sapiens (human)
response to peptide hormoneLeukotriene A-4 hydrolaseHomo sapiens (human)
type I pneumocyte differentiationLeukotriene A-4 hydrolaseHomo sapiens (human)
brain developmentEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
heart developmentEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
cardioblast differentiationEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
methylationEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
protein processingEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
angiogenesisAminopeptidase NHomo sapiens (human)
cell differentiationAminopeptidase NHomo sapiens (human)
symbiont entry into host cellAminopeptidase NHomo sapiens (human)
proteolysisAminopeptidase NHomo sapiens (human)
peptide catabolic processAminopeptidase NHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (22)

Processvia Protein(s)Taxonomy
phosphatidylserine bindingNeprilysinHomo sapiens (human)
endopeptidase activityNeprilysinHomo sapiens (human)
metalloendopeptidase activityNeprilysinHomo sapiens (human)
protein bindingNeprilysinHomo sapiens (human)
exopeptidase activityNeprilysinHomo sapiens (human)
zinc ion bindingNeprilysinHomo sapiens (human)
peptide bindingNeprilysinHomo sapiens (human)
protein homodimerization activityNeprilysinHomo sapiens (human)
oligopeptidase activityNeprilysinHomo sapiens (human)
cardiolipin bindingNeprilysinHomo sapiens (human)
RNA bindingLeukotriene A-4 hydrolaseHomo sapiens (human)
aminopeptidase activityLeukotriene A-4 hydrolaseHomo sapiens (human)
epoxide hydrolase activityLeukotriene A-4 hydrolaseHomo sapiens (human)
leukotriene-A4 hydrolase activityLeukotriene A-4 hydrolaseHomo sapiens (human)
protein bindingLeukotriene A-4 hydrolaseHomo sapiens (human)
peptidase activityLeukotriene A-4 hydrolaseHomo sapiens (human)
zinc ion bindingLeukotriene A-4 hydrolaseHomo sapiens (human)
tripeptide aminopeptidase activityLeukotriene A-4 hydrolaseHomo sapiens (human)
metalloaminopeptidase activityLeukotriene A-4 hydrolaseHomo sapiens (human)
methyltransferase activityEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
metal ion bindingEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
metalloendopeptidase activityEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
virus receptor activityAminopeptidase NHomo sapiens (human)
aminopeptidase activityAminopeptidase NHomo sapiens (human)
metallopeptidase activityAminopeptidase NHomo sapiens (human)
signaling receptor activityAminopeptidase NHomo sapiens (human)
metalloaminopeptidase activityAminopeptidase NHomo sapiens (human)
zinc ion bindingAminopeptidase NHomo sapiens (human)
peptide bindingAminopeptidase NHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (31)

Processvia Protein(s)Taxonomy
cytoplasmNeprilysinHomo sapiens (human)
early endosomeNeprilysinHomo sapiens (human)
trans-Golgi networkNeprilysinHomo sapiens (human)
plasma membraneNeprilysinHomo sapiens (human)
brush borderNeprilysinHomo sapiens (human)
focal adhesionNeprilysinHomo sapiens (human)
synaptic vesicleNeprilysinHomo sapiens (human)
cell surfaceNeprilysinHomo sapiens (human)
membraneNeprilysinHomo sapiens (human)
axonNeprilysinHomo sapiens (human)
dendriteNeprilysinHomo sapiens (human)
secretory granule membraneNeprilysinHomo sapiens (human)
cytoplasmic vesicleNeprilysinHomo sapiens (human)
neuronal cell bodyNeprilysinHomo sapiens (human)
neuron projection terminusNeprilysinHomo sapiens (human)
membrane raftNeprilysinHomo sapiens (human)
synapseNeprilysinHomo sapiens (human)
extracellular exosomeNeprilysinHomo sapiens (human)
presynapseNeprilysinHomo sapiens (human)
plasma membraneNeprilysinHomo sapiens (human)
extracellular regionLeukotriene A-4 hydrolaseHomo sapiens (human)
nucleoplasmLeukotriene A-4 hydrolaseHomo sapiens (human)
cytosolLeukotriene A-4 hydrolaseHomo sapiens (human)
extracellular exosomeLeukotriene A-4 hydrolaseHomo sapiens (human)
tertiary granule lumenLeukotriene A-4 hydrolaseHomo sapiens (human)
ficolin-1-rich granule lumenLeukotriene A-4 hydrolaseHomo sapiens (human)
cytosolLeukotriene A-4 hydrolaseHomo sapiens (human)
nucleusLeukotriene A-4 hydrolaseHomo sapiens (human)
Golgi membraneEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
transport vesicle membraneEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
plasma membraneEEF1AKMT4-ECE2 readthrough transcript proteinHomo sapiens (human)
extracellular spaceAminopeptidase NHomo sapiens (human)
lysosomal membraneAminopeptidase NHomo sapiens (human)
endoplasmic reticulum-Golgi intermediate compartmentAminopeptidase NHomo sapiens (human)
plasma membraneAminopeptidase NHomo sapiens (human)
external side of plasma membraneAminopeptidase NHomo sapiens (human)
secretory granule membraneAminopeptidase NHomo sapiens (human)
extracellular exosomeAminopeptidase NHomo sapiens (human)
cytoplasmAminopeptidase NHomo sapiens (human)
plasma membraneAminopeptidase NHomo sapiens (human)
extracellular spaceAminopeptidase NHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID67194Inhibitory activity against human bronchiolar smooth muscle Endothelin-converting enzyme 11995Journal of medicinal chemistry, Jun-09, Volume: 38, Issue:12
Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle.
AID128885Analgesic effect when injected intracerebroventricularly at 50 (microg)1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
New kelatorphan-related inhibitors of enkephalin metabolism: improved antinociceptive properties.
AID56052Inhibitory activity against Dipeptidyl aminopeptidase using 10 nM of [3H]Leu-enkephalin as substrate1985Journal of medicinal chemistry, Sep, Volume: 28, Issue:9
New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties.
AID56053Inhibition of [3H]Leu-enkephalin binding to Dipeptidyl aminopeptidase (DAP)1988Journal of medicinal chemistry, Sep, Volume: 31, Issue:9
Retro-inverso concept applied to the complete inhibitors of enkephalin-degrading enzymes.
AID223081Inhibitory activity was determined for LTB4 production in human whole blood.2000Journal of medicinal chemistry, Feb-24, Volume: 43, Issue:4
Structure-activity relationship studies on 1-[2-(4-Phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A(4) (LTA(4)) hydrolase.
AID6735750% inhibitory activity against enkephalinase purified from rat kidney with [3H]D-Ala2-Leu-enkephalin (20 nM) as substrate.1985Journal of medicinal chemistry, Sep, Volume: 28, Issue:9
New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties.
AID135425Analgesic effect when injected intracerebroventricularly at 50 (microg)1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
New kelatorphan-related inhibitors of enkephalin metabolism: improved antinociceptive properties.
AID35684Inhibition of [3H]Leu-enkephalin binding to aminopeptidase1988Journal of medicinal chemistry, Sep, Volume: 31, Issue:9
Retro-inverso concept applied to the complete inhibitors of enkephalin-degrading enzymes.
AID99747Inhibitory activity was determined against Leukotriene A4 hydrolase2000Journal of medicinal chemistry, Feb-24, Volume: 43, Issue:4
Structure-activity relationship studies on 1-[2-(4-Phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A(4) (LTA(4)) hydrolase.
AID38380Compound was evaluated for inhibition of enkephalin degrading enzyme, aminopeptidase N(APN)2001Journal of medicinal chemistry, Oct-11, Volume: 44, Issue:21
Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs.
AID147213Inhibitory activity against big ET-1 of Neutral endopeptidase1995Journal of medicinal chemistry, Jun-09, Volume: 38, Issue:12
Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle.
AID213074Inhibitory activity against thermolysin with 0.5 uM [Leu5]-enkephalin (NEN)1995Journal of medicinal chemistry, Jun-09, Volume: 38, Issue:12
Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle.
AID35687Inhibitory activity against aminopeptidase using 10 nM of [3H]Leu-enkephalin as substrate1985Journal of medicinal chemistry, Sep, Volume: 28, Issue:9
New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties.
AID147212Inhibitory activity against Leu-enkeph of Neutral endopeptidase1995Journal of medicinal chemistry, Jun-09, Volume: 38, Issue:12
Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle.
AID147516Inhibition of [3H]Ala2-Leu-enkephalin binding to Neutral endopeptidase (NEP)1988Journal of medicinal chemistry, Sep, Volume: 31, Issue:9
Retro-inverso concept applied to the complete inhibitors of enkephalin-degrading enzymes.
AID147396Compound was evaluated for inhibition of enkephalin degrading enzyme, neutral endopeptidase (NEP)2001Journal of medicinal chemistry, Oct-11, Volume: 44, Issue:21
Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs.
AID1799789Enzymatic Assay from Article 10.1074/jbc.M110.120576: \\Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in vitro and ex vivo enzymatic assay.\\2010The Journal of biological chemistry, Nov-05, Volume: 285, Issue:45
Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in vitro and ex vivo enzymatic assay.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (58)

TimeframeStudies, This Drug (%)All Drugs %
pre-199027 (46.55)18.7374
1990's23 (39.66)18.2507
2000's5 (8.62)29.6817
2010's2 (3.45)24.3611
2020's1 (1.72)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.09

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 weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index10.09 (24.57)
Research Supply Index4.08 (2.92)
Research Growth Index4.17 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.09)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (1.72%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other57 (98.28%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]