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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2020-02-26 21:40:22 UTC
HMDB IDHMDB0014804
Secondary Accession Numbers
  • HMDB14804
Metabolite Identification
Common NameNafarelin
DescriptionNafarelin is only found in individuals that have used or taken this drug. It is a potent synthetic agonist of gonadotropin-releasing hormone with 3-(2-naphthyl)-D-alanine substitution at residue 6. Nafarelin has been used in the treatments of central precocious puberty and endometriosis. [PubChem]Like GnRH, initial or intermittent administration of nafarelin stimulates release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland, which in turn transiently increases production of estradiol in females and testosterone in both sexes. However, with continuous daily administration, nafarelin continuously occupies the GnRH receptor, leading to a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes. This causes a significant and sustained decline in the production of LH and FSH. A decline in gonadotropin production and release causes a dramatic reversible decrease in synthesis of estradiol, progesterone, and testosterone by the ovaries or testes. Like normal endometrium, endometriotic implants contain estrogen receptors. Estrogen stimulates the growth of endometrium. Use of nafarelin induces anovulation and amenorrhea and decreases serum concentrations of estradiol to the postmenopausal range, which induces atrophy of endometriotic implants. However, nafarelin does not abolish the underlying pathophysiology of endometriosis. In children with central precocious puberty receiving nafarelin, serum LH, testosterone, and estradiol concentrations return to prepubertal levels. This results in the supression of secondary sexual characteristics and decrased rate of linear growth and skeletal maturation. Following disconinuation of nafarelin, the effects of the drug is reversed, meaning FSH and LH concentrations usually return to pretreatment levels.
Structure
Data?1582753222
Synonyms
ValueSource
Nafarelin acetateHMDB
Nafarelin acetate, hydrateHMDB
SynarelHMDB
Nafarelin monoacetateHMDB
Chemical FormulaC66H83N17O13
Average Molecular Weight1322.4713
Monoisotopic Molecular Weight1321.635625827
IUPAC NameN-(5-carbamimidamido-1-{2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl}-1-oxopentan-2-yl)-2-{2-[2-(3-hydroxy-2-{2-[3-(1H-imidazol-4-yl)-2-[(5-oxopyrrolidin-2-yl)formamido]propanamido]-3-(1H-indol-3-yl)propanamido}propanamido)-3-(4-hydroxyphenyl)propanamido]-3-(naphthalen-2-yl)propanamido}-4-methylpentanamide
Traditional Namenafarelin
CAS Registry Number76932-56-4
SMILES
CC(C)CC(NC(=O)C(CC1=CC2=CC=CC=C2C=C1)NC(=O)C(CC1=CC=C(O)C=C1)NC(=O)C(CO)NC(=O)C(CC1=CNC2=CC=CC=C12)NC(=O)C(CC1=CNC=N1)NC(=O)C1CCC(=O)N1)C(=O)NC(CCCNC(N)=N)C(=O)N1CCCC1C(=O)NCC(N)=O
InChI Identifier
InChI=1S/C66H83N17O13/c1-36(2)25-48(58(89)76-47(13-7-23-71-66(68)69)65(96)83-24-8-14-54(83)64(95)73-33-55(67)86)77-60(91)50(28-38-15-18-39-9-3-4-10-40(39)26-38)78-59(90)49(27-37-16-19-43(85)20-17-37)79-63(94)53(34-84)82-61(92)51(29-41-31-72-45-12-6-5-11-44(41)45)80-62(93)52(30-42-32-70-35-74-42)81-57(88)46-21-22-56(87)75-46/h3-6,9-12,15-20,26,31-32,35-36,46-54,72,84-85H,7-8,13-14,21-25,27-30,33-34H2,1-2H3,(H2,67,86)(H,70,74)(H,73,95)(H,75,87)(H,76,89)(H,77,91)(H,78,90)(H,79,94)(H,80,93)(H,81,88)(H,82,92)(H4,68,69,71)
InChI KeyRWHUEXWOYVBUCI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
KingdomOrganic compounds
Super ClassOrganic Polymers
ClassPolypeptides
Sub ClassNot Available
Direct ParentPolypeptides
Alternative Parents
Substituents
  • Polypeptide
  • Alpha peptide
  • Tyrosine or derivatives
  • Phenylalanine or derivatives
  • Histidine or derivatives
  • Leucine or derivatives
  • N-acyl-alpha amino acid or derivatives
  • Proline or derivatives
  • Alpha-amino acid amide
  • Triptan
  • Serine or derivatives
  • N-substituted-alpha-amino acid
  • 3-alkylindole
  • Alpha-amino acid or derivatives
  • Naphthalene
  • Amphetamine or derivatives
  • Indole or derivatives
  • Indole
  • Pyrrolidine carboxylic acid or derivatives
  • N-acylpyrrolidine
  • Pyrrolidine-2-carboxamide
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Monocyclic benzene moiety
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Benzenoid
  • Substituted pyrrole
  • Pyrrolidone
  • 2-pyrrolidone
  • Azole
  • Pyrrolidine
  • Tertiary carboxylic acid amide
  • Pyrrole
  • Imidazole
  • Heteroaromatic compound
  • Primary carboxylic acid amide
  • Carboxamide group
  • Guanidine
  • Lactam
  • Secondary carboxylic acid amide
  • Carboximidamide
  • Organoheterocyclic compound
  • Azacycle
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organooxygen compound
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Alcohol
  • Primary alcohol
  • Organonitrogen compound
  • Organic oxygen compound
  • Imine
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.017 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.017 g/LALOGPS
logP1.21ALOGPS
logP-2.7ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)9.49ChemAxon
pKa (Strongest Basic)11.92ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count17ChemAxon
Polar Surface Area472.13 ŲChemAxon
Rotatable Bond Count33ChemAxon
Refractivity357.8 m³·mol⁻¹ChemAxon
Polarizability137.29 ųChemAxon
Number of Rings8ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dr-9037302120-f0facb1967d30439597dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9011200000-e32adcd953ac1c721212Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00e9-9011100000-0e896538a04b95abd857Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0ukc-2194100000-e5cb37d2eafc7e73ef96Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-11b9-6595010100-3cfda325f415bde10f61Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9410011130-eb97257a1937988394bcSpectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00666 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00666 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID10605761
KEGG Compound IDC07613
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNafarelin
METLIN IDNot Available
PubChem Compound25077649
PDB IDNot Available
ChEBI ID7445
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Burry KA: Nafarelin in the management of endometriosis: quality of life assessment. Am J Obstet Gynecol. 1992 Feb;166(2):735-9. [PubMed:1531576 ]
  2. Henzl MR: Gonadotropin-releasing hormone analogs: update on new findings. Am J Obstet Gynecol. 1992 Feb;166(2):757-61. [PubMed:1531579 ]
  3. Saltiel E, Garabedian-Ruffalo SM: Pharmacologic management of endometriosis. Clin Pharm. 1991 Jul;10(7):518-31. [PubMed:1830521 ]
  4. Chrisp P, Goa KL: Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. Drugs. 1990 Apr;39(4):523-51. [PubMed:2140979 ]
  5. Letassy NA, Thompson DF, Britton ML, Suda RR Sr: Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis. DICP. 1990 Dec;24(12):1204-9. [PubMed:2151003 ]
  6. Garner C: Uses of GnRH agonists. J Obstet Gynecol Neonatal Nurs. 1994 Sep;23(7):563-70. [PubMed:7996307 ]
  7. Hugues JN, Cedrin Durnerin IC: Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins. Hum Reprod Update. 1998 Jan-Feb;4(1):83-101. [PubMed:9622415 ]

Enzymes

General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle- stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol- calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling
Gene Name:
GNRHR
Uniprot ID:
P30968
Molecular weight:
37730.4
References
  1. Barbieri RL: Comparison of the pharmacology of nafarelin and danazol. Am J Obstet Gynecol. 1990 Feb;162(2):581-5. [PubMed:2137975 ]
  2. Suh J, Lee E, Hwang S, Yoon S, Yoon BK, Bae D, Choi D: Dose of GnRH agonist (nafarelin acetate) affects intrafollicular PAPP-A expression in controlled ovarian hyperstimulation cycle. Eur J Obstet Gynecol Reprod Biol. 2004 Jan 15;112(1):65-8. [PubMed:14687742 ]
  3. Valle RF, Sciarra JJ: Endometriosis: treatment strategies. Ann N Y Acad Sci. 2003 Nov;997:229-39. [PubMed:14644830 ]
  4. Batzer FR: GnRH analogs: options for endometriosis-associated pain treatment. J Minim Invasive Gynecol. 2006 Nov-Dec;13(6):539-45. [PubMed:17097577 ]
  5. Hugues JN, Cedrin Durnerin IC: Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins. Hum Reprod Update. 1998 Jan-Feb;4(1):83-101. [PubMed:9622415 ]
  6. Garner C: Uses of GnRH agonists. J Obstet Gynecol Neonatal Nurs. 1994 Sep;23(7):563-70. [PubMed:7996307 ]
  7. Saltiel E, Garabedian-Ruffalo SM: Pharmacologic management of endometriosis. Clin Pharm. 1991 Jul;10(7):518-31. [PubMed:1830521 ]
  8. Chrisp P, Goa KL: Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. Drugs. 1990 Apr;39(4):523-51. [PubMed:2140979 ]
  9. Letassy NA, Thompson DF, Britton ML, Suda RR Sr: Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis. DICP. 1990 Dec;24(12):1204-9. [PubMed:2151003 ]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for gonadotropin releasing hormone II (GnRH II). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (Potential)
Gene Name:
GNRHR2
Uniprot ID:
Q96P88
Molecular weight:
19031.1
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Valle RF, Sciarra JJ: Endometriosis: treatment strategies. Ann N Y Acad Sci. 2003 Nov;997:229-39. [PubMed:14644830 ]
  4. Barbieri RL: Comparison of the pharmacology of nafarelin and danazol. Am J Obstet Gynecol. 1990 Feb;162(2):581-5. [PubMed:2137975 ]
  5. Suh J, Lee E, Hwang S, Yoon S, Yoon BK, Bae D, Choi D: Dose of GnRH agonist (nafarelin acetate) affects intrafollicular PAPP-A expression in controlled ovarian hyperstimulation cycle. Eur J Obstet Gynecol Reprod Biol. 2004 Jan 15;112(1):65-8. [PubMed:14687742 ]
  6. Batzer FR: GnRH analogs: options for endometriosis-associated pain treatment. J Minim Invasive Gynecol. 2006 Nov-Dec;13(6):539-45. [PubMed:17097577 ]
  7. Hugues JN, Cedrin Durnerin IC: Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins. Hum Reprod Update. 1998 Jan-Feb;4(1):83-101. [PubMed:9622415 ]
  8. Garner C: Uses of GnRH agonists. J Obstet Gynecol Neonatal Nurs. 1994 Sep;23(7):563-70. [PubMed:7996307 ]
  9. Saltiel E, Garabedian-Ruffalo SM: Pharmacologic management of endometriosis. Clin Pharm. 1991 Jul;10(7):518-31. [PubMed:1830521 ]
  10. Chrisp P, Goa KL: Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. Drugs. 1990 Apr;39(4):523-51. [PubMed:2140979 ]
  11. Letassy NA, Thompson DF, Britton ML, Suda RR Sr: Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis. DICP. 1990 Dec;24(12):1204-9. [PubMed:2151003 ]