Page last updated: 2024-12-07

phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide

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Description

phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide: endogenous opioid antagonist octapeptide from bovine brain [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID123797
SCHEMBL ID3539226
MeSH IDM0151925
PubMed CID9854861
CHEMBL ID429731
MeSH IDM0151925

Synonyms (37)

Synonym
fmrfamide-like octapeptide
f-8-f-nh2
f8famide
phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
ff8 (morphine modulating peptide)
octapeptide f8fa
flfqpqrf-nh2
f-8-f-amide
phe-leu-phe-gln-pro-gln-arg-phe-nh2
morphine modulating neuropeptide
npff
l-phenylalaninamide, l-phenylalanyl-l-leucyl-l-phenylalanyl-l-glutaminyl-l-prolyl-l-glutaminyl-l-arginyl-
(2s)-2-[[(2s)-1-[(2s)-5-amino-2-[[(2s)-2-[[(2s)-2-[(2-amino-3-phenylpropanoyl)amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-n-[(2s)-1-[(1-amino-1-oxo-3-phenylpropan-2-yl)amino]-5-(diaminomethylidenea
SCHEMBL3539226
2-{[1-(2-{2-[2-(2-amino-3-phenyl-propionylamino)-4-methyl-pentanoylamino]-3-phenyl-propionylamino}-4-carbamoyl-butyryl)-pyrrolidine-2-carbonyl]-amino}-pentanedioic acid 5-amide 1-{[1-(1-carbamoyl-2-phenyl-ethylcarbamoyl)-4-guanidino-butyl]-amide}
bdbm50037557
neuropeptide ff ,
phe-leu-phe-gln-pro-gln-arg-phe amide, >=95% (hplc)
NCGC00167257-01
CHEMBL429731 ,
prrp31
cas_235433-36-0
bdbm86139
cas_99566-27-5
npsf
99566-27-5
[125i]-npff
[125i]npff
[125i]-neuropeptide ff
gtpl3797
AKOS024457451
mfcd00076704
phe-leu-phe-gln-pro-gln-arg-phe-amide
HY-P1248
CS-0029121
neuropeptide ff(cattle)(9ci)
MS-31938

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" ESI clearly outperformed APCI in limits of detection, and was the method of choice for coupling with narrow-bore reversed-phase liquid chromatography to assess the pharmacokinetic profile and brain concentration of the neuropeptide FF antagonist in experimental animals."( Exploratory pharmacokinetics and brain distribution study of a neuropeptide FF antagonist by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry.
Janáky, T; Prokai, L; Prokai-Tatrai, K; Zharikova, AD, 2000
)
0.31

Bioavailability

ExcerptReferenceRelevance
" This study indicated a rapid disappearance of dansyl-Pro-Gln-Arg-NH(2) from the plasma and the brain, and modest CNS bioavailability after intravenous administration to rats."( Exploratory pharmacokinetics and brain distribution study of a neuropeptide FF antagonist by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry.
Janáky, T; Prokai, L; Prokai-Tatrai, K; Zharikova, AD, 2000
)
0.31
" To develop stable and orally bioavailable analogues of DN-9, eight lactam-bridged cyclic analogues of DN-9 between positions 2 and 5 were designed, synthesized, and biologically evaluated."( Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
Chen, D; Fang, Q; Li, N; Niu, J; Shi, X; Shi, Y; Xiao, J; Xu, B; Xu, K; Zhang, M; Zhang, Q; Zhang, R, 2021
)
0.62

Dosage Studied

ExcerptRelevanceReference
" Dose-response curves for 1DMe in the presence of naltrindole or naltrexone, delta- and mu-opioid selective antagonists respectively, indicate that 1DMe preferentially reversed mu-receptor-mediated but increased delta-receptor-mediated analgesia."( Differential modulation of mu- and delta-opioid antinociception by neuropeptide FF receptors in young mice.
Desprat, C; Zajac, JM, 1997
)
0.3
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (5)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
phosphopantetheinyl transferaseBacillus subtilisPotency56.23410.141337.9142100.0000AID1490
DNA polymerase kappa isoform 1Homo sapiens (human)Potency29.93490.031622.3146100.0000AID588579
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Neuropeptide FF receptor 2Mus musculus (house mouse)Ki0.00110.00110.00110.0011AID1820164
Neuropeptide FF receptor 1Homo sapiens (human)Ki0.00010.00010.02070.0580AID1820160
Neuropeptide FF receptor 2Homo sapiens (human)Ki0.00060.00000.05970.2500AID1289950; AID1820161
[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)
Neuropeptide FF receptor 1Homo sapiens (human)EC50 (µMol)0.23600.07100.99024.7000AID1536344; AID1812980
Neuropeptide FF receptor 1Homo sapiens (human)Kd0.00110.00110.01100.0209AID1740813
Neuropeptide FF receptor 2Homo sapiens (human)EC50 (µMol)0.12430.00270.19260.6120AID1536316; AID1740822; AID1812982; AID697926; AID697929; AID697932; AID697935; AID697938; AID697941; AID697944
Neuropeptide FF receptor 2Homo sapiens (human)Kd0.00030.00020.00030.0004AID1740814; AID1740893
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (6)

Processvia Protein(s)Taxonomy
neuropeptide signaling pathwayNeuropeptide FF receptor 1Homo sapiens (human)
biological_processNeuropeptide FF receptor 1Homo sapiens (human)
G protein-coupled receptor signaling pathwayNeuropeptide FF receptor 1Homo sapiens (human)
cellular response to hormone stimulusNeuropeptide FF receptor 1Homo sapiens (human)
neuropeptide signaling pathwayNeuropeptide FF receptor 2Homo sapiens (human)
detection of abiotic stimulusNeuropeptide FF receptor 2Homo sapiens (human)
regulation of MAPK cascadeNeuropeptide FF receptor 2Homo sapiens (human)
cellular response to hormone stimulusNeuropeptide FF receptor 2Homo sapiens (human)
G protein-coupled receptor signaling pathwayNeuropeptide FF receptor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
G protein-coupled receptor activityNeuropeptide FF receptor 1Homo sapiens (human)
protein bindingNeuropeptide FF receptor 1Homo sapiens (human)
neuropeptide receptor activityNeuropeptide FF receptor 1Homo sapiens (human)
peptide bindingNeuropeptide FF receptor 1Homo sapiens (human)
G protein-coupled receptor activityNeuropeptide FF receptor 2Homo sapiens (human)
neuropeptide receptor activityNeuropeptide FF receptor 2Homo sapiens (human)
opioid receptor bindingNeuropeptide FF receptor 2Homo sapiens (human)
peptide bindingNeuropeptide FF receptor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
plasma membraneNeuropeptide FF receptor 1Homo sapiens (human)
ciliumNeuropeptide FF receptor 1Homo sapiens (human)
plasma membraneNeuropeptide FF receptor 1Homo sapiens (human)
plasma membraneNeuropeptide FF receptor 2Homo sapiens (human)
actin cytoskeletonNeuropeptide FF receptor 2Homo sapiens (human)
plasma membraneNeuropeptide FF receptor 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (42)

Assay IDTitleYearJournalArticle
AID697937Ratio of EC50 for human NPFF2 receptor F5.34A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1812980Agonist activity at NPFF1R (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by compet2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1536316Agonist activity at NPFF2 receptor (unknown origin) expressed in HEK293A cells assessed as inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins
AID697943Ratio of EC50 for human NPFF2 receptor E5.27A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1820161Displacement of [125I]-1DMeNPFF from recombinant human NPFF2 receptor expressed in CHO cells by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID697928Agonist activity at human NPFF2 receptor Y7.33A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697935Agonist activity at human NPFF2 receptor D6.59A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697930Agonist activity at human NPFF2 receptor H/Q6.69A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1536344Agonist activity at NPFF1 receptor (unknown origin) expressed in HEK293A cells assessed as inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins
AID697936Agonist activity at human NPFF2 receptor F5.34A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697939Agonist activity at human NPFF2 receptor Y5.38A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697942Agonist activity at human NPFF2 receptor E5.27A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697926Agonist activity at human NPFF2 receptor F/Y7.35A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1820163Displacement of [125I]-1DMeNPFF from mouse NPFF1 receptor by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1740893Binding affinity to human NPFFR22020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID1740813Binding affinity to human NPFFR1 expressed in green monkey COS-7 cell membranes by [125I]-1DMeNPFF radioligand based saturation binding assay2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID697932Agonist activity at human NPFF2 receptor H/Q6.69A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1740821Displacement of [125I]-1DMe from NPFF receptor in Sprague-Dawley rat dorsal horn of spinal cord incubated for 150 mins by autoradiography2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID1740820Reversal of morphine-induced analgesia in icv dosed CDF1 mouse assessed as minimum effective dose measured after 15 mins by tail-flick test2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID697934Ratio of EC50 for human NPFF2 receptor D6.59A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697938Agonist activity at human NPFF2 receptor F5.34A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID133092Minimum effective dose able to significantly reverse morphine analgesia in male CDF1 mice by tail-flick test1994Journal of medicinal chemistry, Oct-14, Volume: 37, Issue:21
Structure-activity study of neuropeptide FF: contribution of N-terminal regions to affinity and activity.
AID1820162Selectivity ratio of Ki for displacement of [125I]-1DMeNPFF from human NPFF2 receptor expressed in CHO cells to Ki for displacement of [125I]-1DMeNPFF from human NPFF1 receptor expressed in CHO cells2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID697944Agonist activity at human NPFF2 receptor E5.27A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1812981Agonist activity at NPFF1R (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation by measuring maximal efficacy preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin a2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID697929Agonist activity at human NPFF2 receptor Y7.33A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697925Ratio of EC50 for human NPFF2 receptor F/Y7.35A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697931Ratio of EC50 for human NPFF2 receptor H/Q6.69A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1812982Agonist activity at NPFF2R (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by compet2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID697941Agonist activity at human NPFF2 receptor Y5.38A mutant assessed as [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1820164Displacement of [125I]-1DMeNPFF from mouse NPFF2R receptor by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1740814Binding affinity to human NPFFR2 expressed in green monkey COS-7 cell membranes by [125I]-1DMeNPFF radioligand based saturation binding assay2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID697927Ratio of EC50 for human NPFF2 receptor Y7.33A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1740822Agonist activity at human NPFFR2 expressed in CHO cells assessed as inhibition of forskolin-induced intracellular cyclic cAMP accumulation2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID146419Binding affinity for NPPF receptor in rat spinal cord membranes using the radioligand [125I]-[Tyr1]NPFF1994Journal of medicinal chemistry, Oct-14, Volume: 37, Issue:21
Structure-activity study of neuropeptide FF: contribution of N-terminal regions to affinity and activity.
AID1812983Agonist activity at NPFF2R (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation by measuring maximal efficacy preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin a2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1820160Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1740819Displacement of [125I][Tyr1]-NPFF from NPFF receptor in rat spinal cord membranes by Cheng-Prusoff analysis2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID1289950Displacement of [3H]EYE from human NPFF2 receptor expressed in CHO cell membranes after 1 hr by liquid scintillation spectrophotometric counting2016Journal of medicinal chemistry, Mar-10, Volume: 59, Issue:5
Mimicking of Arginine by Functionalized N(ω)-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples.
AID697940Ratio of EC50 for human NPFF2 receptor Y5.38A mutant to EC50 for human wild type NPFF2 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697933Agonist activity at human NPFF2 receptor D6.59A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID697924Agonist activity at human NPFF2 receptor F/Y7.35A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPFF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (260)

TimeframeStudies, This Drug (%)All Drugs %
pre-19905 (1.92)18.7374
1990's98 (37.69)18.2507
2000's90 (34.62)29.6817
2010's43 (16.54)24.3611
2020's24 (9.23)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.40

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 Index10.40 (24.57)
Research Supply Index5.62 (2.92)
Research Growth Index6.02 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.40)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Trials0 (0.00%)5.53%
Reviews19 (6.88%)6.00%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Observational0 (0.00%)0.25%
Other257 (93.12%)84.16%
Other7 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]