Page last updated: 2024-11-07

enkephalin, ser(2), leu(5), thr(6)-

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

Description

This is a modified form of the endogenous opioid peptide, leucine enkephalin. It is a potent analgesic that has been studied for its potential therapeutic benefits in pain management. This modification involves the substitution of threonine for the original amino acid at position 6. This modification can significantly alter the peptide's pharmacological properties. While the exact mechanism of its action is still under investigation, it is believed to interact with opioid receptors, particularly delta receptors, in the central nervous system. Research has shown that this modification may have increased potency and selectivity compared to the unmodified leucine enkephalin.'
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enkephalin, Ser(2), Leu(5), Thr(6)-: specific probe for the delta-opiate receptor subtype in brain membranes [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID107847
CHEMBL ID124283
CHEBI ID176958
MeSH IDM0105856

Synonyms (40)

Synonym
(2s,3r)-2-[[(2s)-2-[[(2s)-2-[[2-[[(2r)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoic acid
CHEBI:176958
[d-ser2, leu5, thr6]-enkephalin
gtpl1609
dslet
leu-enkephalin, ser(2)-thr-
leucine-enkephalin, ser(2)-thr-
enkephalin-leu, seryl(2)-threonine-
2-ser-thr-leu-enkephalin
l-threonine, l-tyrosyl-d-serylglycyl-l-phenylalanyl-l-leucyl-
dislet
ser(2)-leu(5)-enkephalin-thr(6)
tyrosyl-seryl-glycyl-phenylalanyl-leucyl-threonine
enkephalin-leu, ser(2)-thr-
tyr-ser-gly-phe-leu-thr
dstle
l-threonine, n-(n-(n-(n-(n-l-tyrosyl-d-seryl)glycyl)-l-phenylalanyl)-l-leucyl)-
75644-90-5
CHEMBL124283 ,
bdbm50018708
tyr-d-ser-gly-phe-leu-thr
dslet-oh
enkephalin, ser(2), leu(5), thr(6)-
d-ser2,thr6-leucine-enkephalin
d-ser(2), leu(5), thr(6)-enkephalin
ser(2), leu(5), thr(6)-enkephalin
enkephalin, d-ser(2), leu(5), thr(6)-
C20165
[d-ser2,leu5]enkephalin-thr6
AKOS024456434
(d-ser2)-leu-enkephalin-thr (h-l-tyr-d-ser-gly-l-phe-l-leu-l-thr-oh)
mfcd00076707
h-tyr-d-ser-gly-phe-leu-thr-oh
(2s,5s,8s,14r,17s)-17-amino-8-benzyl-2-((r)-1-hydroxyethyl)-14-(hydroxymethyl)-18-(4-hydroxyphenyl)-5-isobutyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazaoctadecan-1-oic acid
DTXSID00997082
n-[14-amino-5-benzyl-1,4,7,10,13-pentahydroxy-11-(hydroxymethyl)-15-(4-hydroxyphenyl)-2-(2-methylpropyl)-3,6,9,12-tetraazapentadeca-3,6,9,12-tetraen-1-ylidene]threonine
Q27077121
ysgflt
CS-0029454
HY-P1332

Research Excerpts

Dosage Studied

ExcerptRelevanceReference
" Regression analyses failed to reflect significant shifts in the dose-response functions for either agonist on either measure."( Gender effects and central opioid analgesia.
Bodnar, RJ; Kepler, KL; Kest, B; Pasternak, GW; Paul, D; Standifer, KM, 1991
)
0.28
") injected 1 min before each agonist produced a significant parallel shift to the right of the dose-response curves for morphine and DAMGO, but only partly antagonized the effects of DADLE and DSLET."( Role of peripheral mu, delta and kappa opioid receptors in opioid-induced inhibition of gastrointestinal transit in rats.
La Regina, A; Petrillo, P; Sbacchi, M; Tavani, A, 1990
)
0.28
" Naloxonazine shifted the supraspinal DAGO dose-response curve 4-fold to the right without changing the curve for spinal DAGO."( Different mu receptor subtypes mediate spinal and supraspinal analgesia in mice.
Bodnar, RJ; Gistrak, MA; Pasternak, GW; Paul, D, 1989
)
0.28
" In an effort to examine the receptor subtypes responsible for opioid analgesia in specific brain regions, we examined dose-response relationships and naloxonazine sensitivity of morphine and two enkephalin derivatives in the above 4 brain regions."( Role of mu 1-opiate receptors in supraspinal opiate analgesia: a microinjection study.
Bodnar, RJ; Lee, SJ; Pasternak, GW; Williams, CL, 1988
)
0.27
" Respiratory frequency was dose-dependently depressed by FK-33824 and DADLE ; dose-response curves with morphine and D-Ser2- Thr6 could not be obtained for technical reasons."( A comparative study in rats of the respiratory depression and analgesia induced by mu- and delta-opioid agonists.
Flórez, J; Pazos, A, 1984
)
0.27
" Morphine analgesia was inhibited by dynorphin as shown by a rightward shift of the morphine dose-response curve."( Antianalgesic action of dynorphin A mediated by spinal cholecystokinin.
Fujimoto, JM; Holmes, BB; Rady, JJ, 1999
)
0.3
" Both shifted the dose-response curve of morphine to the right and these actions were eliminated by intrathecal PGD(2."( Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice.
Campbell, WB; Fujimoto, JM; Rady, JJ, 2001
)
0.31
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
oligopeptideA peptide containing a relatively small number of amino acids.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Delta-type opioid receptorRattus norvegicus (Norway rat)Ki0.00480.00000.60689.2330AID149938
Mu-type opioid receptorRattus norvegicus (Norway rat)Ki0.03100.00000.38458.6000AID151897
[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)
Delta-type opioid receptorRattus norvegicus (Norway rat)Activity0.09300.00000.11931.2200AID310939
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (26)

Assay IDTitleYearJournalArticle
AID132841Inhibition of electrically evoked contraction of guinea pig ileum (myenteric plexus;longitudinal muscle)[agonist action at mu 1 opioid receptors) and inhibition of electrically evoked contraction of mouse vas deferens (agonist action at delta 1 opioid rec1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID125747Analgesic potency in mice after icv injection and 10 min before exposing to hot plate1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID151592Inhibition of [3H]DAGO binding to mu 1 opioid receptor in rat brain membranes1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID149938Inhibition of [3H]DTLET binding torat brain membrane Opioid receptor delta 11988Journal of medicinal chemistry, Oct, Volume: 31, Issue:10
Development of conformationally constrained linear peptides exhibiting a high affinity and pronounced selectivity for delta opioid receptors.
AID141489Tested for inhibitory concentration against [3H]DAMGO binding at sites of mu-opioid receptor in guinea pig brain membrane1994Journal of medicinal chemistry, Sep-02, Volume: 37, Issue:18
Isothiocyanate-substituted kappa-selective opioid receptor ligands derived from N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl] phenylacetamide.
AID132839Inhibitory potency evaluated against electrically evoked contractions of mouse vas deferens1988Journal of medicinal chemistry, Oct, Volume: 31, Issue:10
Development of conformationally constrained linear peptides exhibiting a high affinity and pronounced selectivity for delta opioid receptors.
AID232698Selectivity ratio of Ki of [3H]-DSLET to Ki of [3H]DAGO; relative inhibition at opioid receptor subtype delta 1 versus mu 11988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID149646Inhibition of [3H]DSLET binding to delta 1 opioid receptors in rat brain membranes1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID138356Inhibitory activity before protection from beta-CNS-induced inactivation in MVD1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID149865Inhibition of electrically evoked contraction of guinea pig ileum (myenteric plexus:longitudinal muscle preparation) by antagonist action at mu 1 opioid receptors1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID231531Ratio of binding affinity towards Mu receptor to that of Delta receptor1988Journal of medicinal chemistry, Oct, Volume: 31, Issue:10
Development of conformationally constrained linear peptides exhibiting a high affinity and pronounced selectivity for delta opioid receptors.
AID76226Inhibitory potency evaluated against electrically evoked contractions of guinea pig ileum1988Journal of medicinal chemistry, Oct, Volume: 31, Issue:10
Development of conformationally constrained linear peptides exhibiting a high affinity and pronounced selectivity for delta opioid receptors.
AID138355Inhibitory activity after protection from beta-CNS-induced inactivation in MVD1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID229264Ratio of IC50 for MVD to GPI1988Journal of medicinal chemistry, Oct, Volume: 31, Issue:10
Development of conformationally constrained linear peptides exhibiting a high affinity and pronounced selectivity for delta opioid receptors.
AID149749Tested for inhibitory concentration against [3H]DPDPE binding at sites of delta-opioid receptor in guinea pig brain membrane1994Journal of medicinal chemistry, Sep-02, Volume: 37, Issue:18
Isothiocyanate-substituted kappa-selective opioid receptor ligands derived from N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl] phenylacetamide.
AID148691Tested for inhibitory concentration against [3H]U-69593 binding at sites of kappa-opioid receptor in guinea pig brain membrane1994Journal of medicinal chemistry, Sep-02, Volume: 37, Issue:18
Isothiocyanate-substituted kappa-selective opioid receptor ligands derived from N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl] phenylacetamide.
AID148620Tested for inhibitory concentration against [3H]bremazocine binding to total sites of opioid receptor in guinea pig brain membrane1994Journal of medicinal chemistry, Sep-02, Volume: 37, Issue:18
Isothiocyanate-substituted kappa-selective opioid receptor ligands derived from N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl] phenylacetamide.
AID148510Effective dose required for antagonistic activity against Opioid receptor delta 1 24 hr after icv administration of 10 nmol of NTII by using abdominal stretch assay1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
Naltrindole 5'-isothiocyanate: a nonequilibrium, highly selective delta opioid receptor antagonist.
AID232679Selectivity ratio, inhibition of electrically evoked contraction (IC50) of mouse vas deferens (MVD) versus guinea pig ileum (GPI)1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Investigation of the structural parameters involved in the mu and delta opioid receptor discrimination of linear enkephalin-related peptides.
AID151897Inhibition of [3H]DAGO binding to rat brain membrane Opioid receptor mu 11988Journal of medicinal chemistry, Oct, Volume: 31, Issue:10
Development of conformationally constrained linear peptides exhibiting a high affinity and pronounced selectivity for delta opioid receptors.
AID133526Selectivity against Opioid receptor delta 2 in the presence of 0.5 nmol icv SIOM1993Journal of medicinal chemistry, Aug-20, Volume: 36, Issue:17
A selective delta 1 opioid receptor agonist derived from oxymorphone. Evidence for separate recognition sites for delta 1 opioid receptor agonists and antagonists.
AID310938Agonist activity at rat delta opioid receptor expressed in C6 cells assessed as stimulation of [35S]GTP-gamma-S binding relative to BW373U862007Journal of medicinal chemistry, Apr-19, Volume: 50, Issue:8
Quantitative conformationally sampled pharmacophore for delta opioid ligands: reevaluation of hydrophobic moieties essential for biological activity.
AID310939Displacement of [3H]naltrindole from rat delta opioid receptor expressed in C6 cells2007Journal of medicinal chemistry, Apr-19, Volume: 50, Issue:8
Quantitative conformationally sampled pharmacophore for delta opioid ligands: reevaluation of hydrophobic moieties essential for biological activity.
AID1346361Human delta receptor (Opioid receptors)1998NIDA research monograph, Mar, Volume: 178Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.
AID1346373Mouse delta receptor (Opioid receptors)1994Molecular pharmacology, Feb, Volume: 45, Issue:2
Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.
AID1346364Human mu receptor (Opioid receptors)1998NIDA research monograph, Mar, Volume: 178Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (213)

TimeframeStudies, This Drug (%)All Drugs %
pre-199065 (30.52)18.7374
1990's121 (56.81)18.2507
2000's20 (9.39)29.6817
2010's7 (3.29)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: 8.91

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 Index8.91 (24.57)
Research Supply Index5.42 (2.92)
Research Growth Index4.33 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (8.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews2 (0.89%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other222 (99.11%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]