Page last updated: 2024-11-13

RF9

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

Cross-References

ID SourceID
PubMed CID53320361
CHEMBL ID1672380
CHEBI ID140980
SCHEMBL ID18041259

Synonyms (25)

Synonym
gtpl1486
876310-60-0
n(2)-(tricyclo[3.3.1.1(3,7)]decan-1-ylcarbonyl)-l-arginyl-l-phenylalaninamide
RF9 ,
CHEBI:140980
1-adamantanecarbonyl-arg-phe-nh2
rf 9
CHEMBL1672380 ,
1-adamantanecarbonyl-rf-nh2
adamantane-1-carboxylic acid [(s)-1-((s)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-4-guanidino-butyl]-amide
bdbm50336912
rf9 trifluoroacetate salt
SCHEMBL18041259
AKOS024457741
CS-7903
NCGC00485847-01
HY-107382
Q27088538
2-adamantanecarbonyl-arg-phe-nh2 trifluoroacetate
D93586
AS-77961
PD045604
PD119376
DTXSID001151466
n2-(tricyclo[3.3.1.13,7]dec-1-ylcarbonyl)-l-arginyl-l-phenylalaninamide

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
neuropeptide FF receptor antagonistAn antagonist that binds to and deactivates neuropeptide FF receptors.
neuropeptide FF receptor agonistAn agonist that activates neuropeptide FF (NPFF) receptors.
kisspeptin receptor agonistAn agonist that acts at the kisspeptin receptor (KISS1R).
[role 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]

Drug Classes (1)

ClassDescription
dipeptideAny molecule that contains two amino-acid residues connected by peptide linkages.
[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 (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
KiSS-1 receptorHomo sapiens (human)IC50 (µMol)0.83000.00011.55678.5100AID570382
Neuropeptide FF receptor 1Homo sapiens (human)IC50 (µMol)0.41000.00470.20730.4100AID1536314
Neuropeptide FF receptor 1Homo sapiens (human)Ki0.03130.00010.02070.0580AID1740832; AID1820160; AID718799
Neuropeptide FF receptor 2Homo sapiens (human)IC50 (µMol)0.41000.07600.24300.4100AID1536315
Neuropeptide FF receptor 2Homo sapiens (human)Ki0.04530.00000.05970.2500AID1740833; AID1820161; AID718796
[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)
Mas-related G-protein coupled receptor member X1Mus musculus (house mouse)EC50 (µMol)0.31620.25120.34220.5012AID1167972
Mas-related G-protein coupled receptor member X1Rattus norvegicus (Norway rat)EC50 (µMol)6.30960.30003.30886.3096AID1167971
Mas-related G-protein coupled receptor member X1Homo sapiens (human)EC50 (µMol)100.00000.05000.42220.7943AID1167970
Neuropeptide FF receptor 1Homo sapiens (human)EC50 (µMol)1.74430.07100.99024.7000AID1740837; AID697951; AID698101
Neuropeptide FF receptor 2Homo sapiens (human)EC50 (µMol)0.42550.00270.19260.6120AID697926; AID698097
[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)
Neuropeptide FF receptor 2Homo sapiens (human)Ke0.04500.04500.04500.0450AID1740836
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (10)

Processvia Protein(s)Taxonomy
G protein-coupled receptor signaling pathwayKiSS-1 receptorHomo sapiens (human)
neuropeptide signaling pathwayKiSS-1 receptorHomo sapiens (human)
acute-phase responseMas-related G-protein coupled receptor member X1Homo sapiens (human)
signal transductionMas-related G-protein coupled receptor member X1Homo sapiens (human)
cell surface receptor signaling pathwayMas-related G-protein coupled receptor member X1Homo sapiens (human)
response to chloroquineMas-related G-protein coupled receptor member X1Homo sapiens (human)
G protein-coupled receptor signaling pathwayMas-related G-protein coupled receptor member X1Homo sapiens (human)
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 (7)

Processvia Protein(s)Taxonomy
protein bindingKiSS-1 receptorHomo sapiens (human)
neuropeptide receptor activityKiSS-1 receptorHomo sapiens (human)
G protein-coupled peptide receptor activityKiSS-1 receptorHomo sapiens (human)
transmembrane signaling receptor activityMas-related G-protein coupled receptor member X1Homo sapiens (human)
G protein-coupled receptor activityMas-related G-protein coupled receptor member X1Homo sapiens (human)
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 (6)

Processvia Protein(s)Taxonomy
plasma membraneKiSS-1 receptorHomo sapiens (human)
ciliumKiSS-1 receptorHomo sapiens (human)
cell surfaceKiSS-1 receptorHomo sapiens (human)
membraneKiSS-1 receptorHomo sapiens (human)
intracellular membrane-bounded organelleKiSS-1 receptorHomo sapiens (human)
plasma membraneKiSS-1 receptorHomo sapiens (human)
cell surfaceMas-related G-protein coupled receptor member X1Homo sapiens (human)
plasma membraneMas-related G-protein coupled receptor member X1Homo sapiens (human)
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 (43)

Assay IDTitleYearJournalArticle
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings 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.
AID1347160Primary screen NINDS Rhodamine 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.
AID718800Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells at 500 nM by scintillation counting2012Bioorganic & medicinal chemistry letters, Dec-15, Volume: 22, Issue:24
Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AID698098Agonist activity at human NPFF1 receptor expressed in COS1 cells assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPVF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID1167972Agonist activity at mouse MrgC11 transfected in HEK293 cells by FLIPR assay2014Bioorganic & medicinal chemistry, Nov-01, Volume: 22, Issue:21
Peptidomimetics of Arg-Phe-NH2 as small molecule agonists of Mas-related gene C (MrgC) receptors.
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
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.
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
AID570382Displacement of [125I]kisspeptin-15 from GPR542011ACS medicinal chemistry letters, Jan-13, Volume: 2, Issue:1
Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.
AID706415Activation of NPFF2R in Sprague-Dawley rat cardiac myocytes assessed as effect on cardiac function at 10 nM incubated for 20 mins2012Journal of medicinal chemistry, Sep-13, Volume: 55, Issue:17
Structure-activity studies of RFamide-related peptide-1 identify a functional receptor antagonist and novel cardiac myocyte signaling pathway involved in contractile performance.
AID1536314Antagonist activity at NPFF1 receptor (unknown origin) expressed in HEK293A cells assessed as reversal of NPPF induced inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins
AID1536327Antinociceptive activity in Kunming mouse model of thermal-induced nociception assessed as increase in latency to tail withdrawal at 10 nmol, icv measured up to 60 mins by tail flick test
AID1820186Effect on Luteinizing hormone release in Syrian hamster mouse assessed as increase in LD level at 10 nmol, icv after 30 mins by radioimmunoassay2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1536315Antagonist activity at NPFF2 receptor (unknown origin) expressed in HEK293A cells assessed as reversal of NPPF induced inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins
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.
AID1167970Agonist activity at human MrgX1 transfected in HEK293 cells by FLIPR assay2014Bioorganic & medicinal chemistry, Nov-01, Volume: 22, Issue:21
Peptidomimetics of Arg-Phe-NH2 as small molecule agonists of Mas-related gene C (MrgC) receptors.
AID698101Agonist activity at human NPFF1 receptor expressed in COS1 cells 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.
AID697949Agonist activity at human NPFF1 receptor F/Y7.35A mutant assessed as [3H]inositol phosphate accumulation at 10 uM after 2 hrs by liquid scintillation counting relative to NPVF2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID706416Antagonist activity at NPFF2R in Sprague-Dawley rat cardiac myocytes assessed as attenuation of human RFRP-1-induced reduction in cardiac function at 10 nM incubated for 20 mins2012Journal of medicinal chemistry, Sep-13, Volume: 55, Issue:17
Structure-activity studies of RFamide-related peptide-1 identify a functional receptor antagonist and novel cardiac myocyte signaling pathway involved in contractile performance.
AID697951Agonist activity at human NPFF1 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.
AID697950Ratio of EC50 for human NPFF1 receptor F/Y7.35A mutant to EC50 for human wild type NPFF1 receptor2012Journal of medicinal chemistry, Jul-12, Volume: 55, Issue:13
Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.
AID718798Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF2 receptor expressed in CHO cells at 5 uM by scintillation counting2012Bioorganic & medicinal chemistry letters, Dec-15, Volume: 22, Issue:24
Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AID718801Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells at 5 uM by scintillation counting2012Bioorganic & medicinal chemistry letters, Dec-15, Volume: 22, Issue:24
Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AID698096Agonist activity at human NPFF2 receptor expressed in COS1 cells 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.
AID1740832Displacement of [125I]YVP from human NPFFR1 expressed in CHO cells2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID1536319Effect on neurite outgrowth in mouse Neuro2a cells at 10 uM after 18 hrs by phase contrast microscopic analysis relative to control
AID698097Agonist activity at human NPFF2 receptor expressed in COS1 cells 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.
AID1740836Antagonist activity at human NPFFR2 expressed in green monkey COS1 assessed as antagonist Ke at 7.5 uM incubated for 30 mins by [35S]GTPgammaS binding based scintillation counting method2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID1820185Analgesic activity in NPFF induced C57BL/6N mouse model of analgesia assessed as reversal of NPFF effect on morphine analgesia at 10 nmol, icv2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1167971Agonist activity at rat MrgX1 transfected in HEK293 cells by FLIPR assay2014Bioorganic & medicinal chemistry, Nov-01, Volume: 22, Issue:21
Peptidomimetics of Arg-Phe-NH2 as small molecule agonists of Mas-related gene C (MrgC) receptors.
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
AID718796Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF2 receptor expressed in CHO cells by scintillation counting2012Bioorganic & medicinal chemistry letters, Dec-15, Volume: 22, Issue:24
Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AID1740833Displacement of [125I]Tyr-NPFF from human NPFFR2 expressed in green monkey Cos-1 cells2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID1740837Antagonist activity at human NPFFR1 expressed in CHO cells assessed as reversal of NPVF-induced inhibition of forskolin-stimulated cAMP accumulation incubated for 10 mins by liquid scintillation counting method2020Journal of medicinal chemistry, 11-12, Volume: 63, Issue:21
Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.
AID570392Agonist activity at GPR54 expressed in CHO cells assessed as increase of intracellular calcium mobilization at 10 uM after 1 hr2011ACS medicinal chemistry letters, Jan-13, Volume: 2, Issue:1
Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.
AID718797Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF2 receptor expressed in CHO cells at 500 nM by scintillation counting2012Bioorganic & medicinal chemistry letters, Dec-15, Volume: 22, Issue:24
Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AID1536318Antagonist activity at NPFF2 receptor in mouse Neuro2a cells assessed as inhibition of NPFF-induced neurite outgrowth by measuring neurite outgrowth at 10 uM after 18 hrs by phase contrast microscopic analysis (Rvb = 24.05 +/- 1.19%)
AID718799Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting2012Bioorganic & medicinal chemistry letters, Dec-15, Volume: 22, Issue:24
Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AID1346349Human NPFF2 receptor (Neuropeptide FF/neuropeptide AF receptors)2006Proceedings of the National Academy of Sciences of the United States of America, Jan-10, Volume: 103, Issue:2
RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia.
AID1346421Human NPFF1 receptor (Neuropeptide FF/neuropeptide AF receptors)2006Proceedings of the National Academy of Sciences of the United States of America, Jan-10, Volume: 103, Issue:2
RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (12)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (8.33)29.6817
2010's7 (58.33)24.3611
2020's4 (33.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 40.84

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

MetricThis Compound (vs All)
Research Demand Index40.84 (24.57)
Research Supply Index2.56 (2.92)
Research Growth Index5.63 (4.65)
Search Engine Demand Index60.21 (26.88)
Search Engine Supply Index2.24 (0.95)

This Compound (40.84)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other12 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]