Page last updated: 2024-12-07

morphiceptin

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Description

Morphiceptin is a synthetic tetrapeptide with the sequence Tyr-D-Ala-Phe-Gly. It is a potent agonist of the mu-opioid receptor, and it has been shown to have analgesic effects in animal models. Morphiceptin is thought to be a promising lead compound for the development of new analgesics. It is studied to understand the structure and function of the mu-opioid receptor and to explore the therapeutic potential of opioid receptor agonists. Morphiceptin is synthesized through standard peptide synthesis methods. It is a valuable tool in opioid research due to its high potency, selectivity, and favorable pharmacokinetic properties.'

morphiceptin: synthetic tetrapeptide with morphinelike activities, highly specific for morphine receptors, but not for enkephalin receptors; is the amide of a fragment of the milk protein beta casein; deproceptin is the D-Pro(4)-isomer; see also related heptapeptide beta-casomorphin; RN given refers to parent cpd(L-Tyr-L-Pro-L-Phe-L-Pro)-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID119303
CHEMBL ID362991
CHEBI ID177741
MeSH IDM0092594

Synonyms (33)

Synonym
CHEBI:177741
(2s)-1-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-n-[(2s)-1-[(2s)-2-carbamoylpyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]pyrrolidine-2-carboxamide
tyr-pro-phe-pro-nh2
b-casomorphin-4-amide
morphiceptin
l-prolinamide, l-tyrosyl-l-prolyl-l-phenylalanyl-
.beta.-casomorphin-4-nh2
h-tyr-pro-phe-pro-nh2
74135-04-9
NCGC00163202-01
deproceptin
nh(4)-tyr-pro-phe-pro-conh(2)
l-tyrosyl-l-prolyl-l-phenylalanyl-l-prolinamide
tyr-pro-phe-pro amide
beta-casomorphine(1-4) amide
tyrosyl-prolyl-phenylalanyl-d-prolinamide
tyr-pro-phe-d-pro-nh2
bdbm50166066
[d-pro4]morphiceptin
CHEMBL362991 ,
97tza8anpc ,
unii-97tza8anpc
beta-casomorphin-4-nh2
beta-casomorphin-4-amide
tyrosyl-prolyl-phenylalanyl-delta-prolinamide
tyr-pro-phe-delta-pro-nh2
DTXSID10995574
n-(1-{2-[hydroxy(imino)methyl]pyrrolidin-1-yl}-1-oxo-3-phenylpropan-2-yl)-1-tyrosylpyrrolidine-2-carboximidic acid
(s)-1-(l-tyrosyl)-n-((s)-1-((s)-2-carbamoylpyrrolidin-1-yl)-1-oxo-3-phenylpropan-2-yl)pyrrolidine-2-carboxamide
MS-29674
HY-P1701
CS-0090884
AKOS040753135

Research Excerpts

Actions

Morphiceptin was found to produce a weak inhibition of the twitch response of the RVD. Morphiceptin did not activate phospholipase C-mediated phosphatidylinositol hydrolysis but did transiently activate (2- to 3-fold) phospholipsase D (PLD)

ExcerptReferenceRelevance
"The morphiceptin was found to produce a weak inhibition of the twitch response of the RVD."( Morphiceptin ( beta-casomorphin (1-4) amide): a peptide opioid antagonist in the field stimulated rat vas deferens.
Day, AR; Freer, RJ; Liao, CS, 1981
)
2.19
"Morphiceptin did not activate phospholipase C-mediated phosphatidylinositol hydrolysis but did transiently activate (2- to 3-fold) phospholipase D (PLD), as measured by phosphatidylethanol formation in neuron cultures derived from embryonic day 6 or day 7 cerebral hemispheres."( Opioid peptides activate phospholipase D and protein kinase C-epsilon in chicken embryo neuron cultures.
Dawson, G; Mangoura, D, 1993
)
1.01

Dosage Studied

ExcerptRelevanceReference
" Analysis of the slopes of the dose-response curves seems to suggest that differences between the activity of these opioid peptides in SHR and WAG rats are based on a difference in the density and affinity of the subpopulation of the opioid receptors in these strains of rats."( Analgesic activity of morphiceptin, beta-casomorphin-4, and deltakephalin in normotensive Wistar-Glaxo and spontaneously hypertensive rats.
Członkowski, A; Widy-Tyszkiewicz, E,
)
0.45
[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 (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Delta-type opioid receptorRattus norvegicus (Norway rat)Ki10.00000.00000.60689.2330AID268520
Mu-type opioid receptorRattus norvegicus (Norway rat)IC50 (µMol)0.05660.00010.887410.0000AID635905
Mu-type opioid receptorRattus norvegicus (Norway rat)Ki0.10750.00000.38458.6000AID239609; AID268517
Mu-type opioid receptorHomo sapiens (human)IC50 (µMol)0.32000.00010.813310.0000AID150417
Mu-type opioid receptorHomo sapiens (human)Ki0.15000.00000.419710.0000AID150419
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Mu-type opioid receptorHomo sapiens (human)EC50 (µMol)0.74130.00000.32639.4000AID1279232
[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)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (35)

Processvia Protein(s)Taxonomy
lipid hydroxylationCytochrome P450 3A4Homo sapiens (human)
lipid metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid catabolic processCytochrome P450 3A4Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid metabolic processCytochrome P450 3A4Homo sapiens (human)
cholesterol metabolic processCytochrome P450 3A4Homo sapiens (human)
androgen metabolic processCytochrome P450 3A4Homo sapiens (human)
estrogen metabolic processCytochrome P450 3A4Homo sapiens (human)
alkaloid catabolic processCytochrome P450 3A4Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 3A4Homo sapiens (human)
calcitriol biosynthetic process from calciolCytochrome P450 3A4Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D metabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D catabolic processCytochrome P450 3A4Homo sapiens (human)
retinol metabolic processCytochrome P450 3A4Homo sapiens (human)
retinoic acid metabolic processCytochrome P450 3A4Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 3A4Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 3A4Homo sapiens (human)
oxidative demethylationCytochrome P450 3A4Homo sapiens (human)
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)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (30)

Processvia Protein(s)Taxonomy
monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
steroid bindingCytochrome P450 3A4Homo sapiens (human)
iron ion bindingCytochrome P450 3A4Homo sapiens (human)
protein bindingCytochrome P450 3A4Homo sapiens (human)
steroid hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
retinoic acid 4-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
oxidoreductase activityCytochrome P450 3A4Homo sapiens (human)
oxygen bindingCytochrome P450 3A4Homo sapiens (human)
enzyme bindingCytochrome P450 3A4Homo sapiens (human)
heme bindingCytochrome P450 3A4Homo sapiens (human)
vitamin D3 25-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
caffeine oxidase activityCytochrome P450 3A4Homo sapiens (human)
quinine 3-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
testosterone 6-beta-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
aromatase activityCytochrome P450 3A4Homo sapiens (human)
vitamin D 24-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1,8-cineole 2-exo-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
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)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (12)

Processvia Protein(s)Taxonomy
cytoplasmCytochrome P450 3A4Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 3A4Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 3A4Homo sapiens (human)
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)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (31)

Assay IDTitleYearJournalArticle
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1279232Agonist activity at human recombinant MOR expressed in CHO cells by calcium mobilization assay2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID635911Antinociceptive activity in icv dosed in Swiss albino mouse assessed as rearing latency by hot plate method2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID150417Inhibitory activity against non-selective opiate receptor2003Bioorganic & medicinal chemistry letters, Mar-24, Volume: 13, Issue:6
Synthesis and binding affinity of neuropeptide Y at opiate receptors.
AID268517Displacement of [3H]DAMGO from mu opioid receptor in Wistar rat brain2006Bioorganic & medicinal chemistry letters, Jul-15, Volume: 16, Issue:14
Opioid receptor binding and antinociceptive activity of the analogues of endomorphin-2 and morphiceptin with phenylalanine mimics in the position 3 or 4.
AID1279236Agonist activity at human recombinant DOR expressed in CHO cells at 1 uM by calcium mobilization assay2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID239609Inhibition of DAMGO (Tyr-[D-Ala]-Gly-[NMe-Phe]-Gly-ol) binding to rat brain mu opioid receptor2005Journal of medicinal chemistry, May-05, Volume: 48, Issue:9
Ligand-based prediction of active conformation by 3D-QSAR flexibility descriptors and their application in 3+3D-QSAR models.
AID515106Displacement of [3H]U69593 from delta opioid receptor in guinea pig brain membrane after 3 hrs by liquid scintillation counting2010European journal of medicinal chemistry, Oct, Volume: 45, Issue:10
Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.
AID635912Antinociceptive activity in icv dosed in Swiss albino mouse assessed as jumping latency by hot plate method2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID268520Displacement of [3H]DPDPE from delta opioid receptor in Wistar rat brain2006Bioorganic & medicinal chemistry letters, Jul-15, Volume: 16, Issue:14
Opioid receptor binding and antinociceptive activity of the analogues of endomorphin-2 and morphiceptin with phenylalanine mimics in the position 3 or 4.
AID1279230Displacement of [3H][Ile5,6]deltorphin-2 from DOR in Wistar rat brain homogenate by scintillation counting analysis2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID361270Binding affinity to recombinant CYP3A4 expressed in Escherichia coli assessed as spectral dissociation constant by spectrophotometric equilibrium binding titration method2007The Journal of biological chemistry, Mar-02, Volume: 282, Issue:9
Multiple sequential steps involved in the binding of inhibitors to cytochrome P450 3A4.
AID635909Half life in Wistar rat brain at 0.5 mM by RP-HPLC analysis2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID234375Selectivity ratio is IC50 value of delta opioid receptor using mouse vas deferens (MVD) to that of mu opioid receptor using guinea pig ileum (GPI)1993Journal of medicinal chemistry, Mar-19, Volume: 36, Issue:6
A topochemical approach to explain morphiceptin bioactivity.
AID635914Antinociceptive activity in Swiss albino mouse assessed as jumping latency at 10 ug, icv after 5 to 10 mins by hot plate method2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID635908Antinociceptive activity in Swiss albino mouse assessed as jumping latency at 10 ug, icv up to 90 mins by hot plate method2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID515107Displacement of [3H]DAMGO from mu opioid receptor in rat brain membrane after 3 hrs by liquid scintillation counting2010European journal of medicinal chemistry, Oct, Volume: 45, Issue:10
Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.
AID515109Selectivity ratio of Ki for delta opioid receptor in guinea pig brain membrane to Ki for mu opioid receptor in rat brain membrane2010European journal of medicinal chemistry, Oct, Volume: 45, Issue:10
Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.
AID1279237Agonist activity at human recombinant KOR expressed in CHO cells at 1 uM by calcium mobilization assay2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID635910Antinociceptive activity in icv dosed in Swiss albino mouse assessed as paw licking latency by hot plate method2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID148641In vitro inhibitory activity against delta opioid receptor using mouse vas deferens (MVD) assay1993Journal of medicinal chemistry, Mar-19, Volume: 36, Issue:6
A topochemical approach to explain morphiceptin bioactivity.
AID1279238Intrinsic activity at human recombinant MOR expressed in CHO cells by calcium mobilization assay relative to dermorphin2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID268521Selectivity for mu opioid receptor over delta opioid receptor2006Bioorganic & medicinal chemistry letters, Jul-15, Volume: 16, Issue:14
Opioid receptor binding and antinociceptive activity of the analogues of endomorphin-2 and morphiceptin with phenylalanine mimics in the position 3 or 4.
AID635907Selectivity ratio of IC50 for delta opioid receptor in Wistar rat brain membrane to IC50 for mu opioid receptor in Wistar rat brain membrane2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID1279231Displacement of [3H]nor-BNI from KOR in Dunkin Hartley guinea pig brain homogenate by scintillation counting analysis2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID635905Displacement of [3H]DAMGO from Wistar rat mu opioid receptor by liquid scintillation counting2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID1279229Displacement of [3H]DAMGO from MOR in Wistar rat brain homogenate by scintillation counting analysis2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID635906Displacement of [3H][Ile5,6]deltorphin 2 from delta opioid receptor in Wistar rat brain membrane by liquid scintillation counting2011Bioorganic & medicinal chemistry, Dec-01, Volume: 19, Issue:23
Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs.
AID150419Binding affinity towards non-selective opiate receptor2003Bioorganic & medicinal chemistry letters, Mar-24, Volume: 13, Issue:6
Synthesis and binding affinity of neuropeptide Y at opiate receptors.
AID224563In vitro inhibitory activity against mu opioid receptor using guinea pig ileum (GPI) assay1993Journal of medicinal chemistry, Mar-19, Volume: 36, Issue:6
A topochemical approach to explain morphiceptin bioactivity.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (125)

TimeframeStudies, This Drug (%)All Drugs %
pre-199050 (40.00)18.7374
1990's37 (29.60)18.2507
2000's24 (19.20)29.6817
2010's9 (7.20)24.3611
2020's5 (4.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 19.91

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

MetricThis Compound (vs All)
Research Demand Index19.91 (24.57)
Research Supply Index4.94 (2.92)
Research Growth Index4.27 (4.65)
Search Engine Demand Index21.17 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (19.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews2 (1.44%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other137 (98.56%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]