ContaminantDB: Nafarelin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (2)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:23 UTC

Update Date

2026-04-05 17:24:07 UTC

Accession Number

CHEM002243

Identification

Common Name

Nafarelin

Class

Small Molecule

Description

Nafarelin 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.

Contaminant Sources

HMDB Contaminants - Urine
T3DB toxins

Contaminant Type

Amide
Amine
Antiendometriotic Agent
Drug
Fertility Agent, Female
Gonadotropin-Releasing Hormone
Gonadotropin-releasing hormone agonist
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Nafarelin acetate	HMDB
Nafarelin acetate, hydrate	HMDB
Synarel	HMDB
Nafarelin monoacetate	HMDB

Chemical Formula

C₆₆H₈₃N₁₇O₁₃

Average Molecular Mass

1322.471 g/mol

Monoisotopic Mass

1321.636 g/mol

CAS Registry Number

76932-56-4

IUPAC Name

N-(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 Name

nafarelin

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 Key

RWHUEXWOYVBUCI-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.

Kingdom

Organic compounds

Super Class

Organic Polymers

Class

Polypeptides

Sub Class

Not Available

Direct Parent

Polypeptides

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

polypeptide (CHEBI:7445 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	1.66e-02 g/L

Predicted Properties

Property	Value	Source
Water Solubility	0.017 g/L	ALOGPS
logP	1.21	ALOGPS
logP	-2.7	ChemAxon
logS	-4.9	ALOGPS
pKa (Strongest Acidic)	9.49	ChemAxon
pKa (Strongest Basic)	11.92	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	17	ChemAxon
Hydrogen Donor Count	17	ChemAxon
Polar Surface Area	472.13 Å²	ChemAxon
Rotatable Bond Count	33	ChemAxon
Refractivity	357.8 m³·mol⁻¹	ChemAxon
Polarizability	137.29 Å³	ChemAxon
Number of Rings	8	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00dr-9037302120-f0facb1967d30439597d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00di-9011200000-e32adcd953ac1c721212	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00e9-9011100000-0e896538a04b95abd857	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0ukc-2194100000-e5cb37d2eafc7e73ef96	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-11b9-6595010100-3cfda325f415bde10f61	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9410011130-eb97257a1937988394bc	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0kg9-0017900031-0ad2341a5a6f67386398	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0abd-1133910111-a355010b703bbfdcb57f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0pbl-1611920110-b8ca31d70aed9fbf9a0e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00dl-1109300000-0c7604e46e8e28bdf55f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0fkl-3829202140-80a733fe94b1819e25e8	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0096-5911304005-08b37dbd696b4e3af318	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Rapidly absorbed into the systemic circulation after intranasal administration. Bioavailability from a 400 µg dose averaged 2.8% (range 1.2 to 5.6%). Not absorbed after oral administration.

Mechanism of Toxicity

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.

Metabolism

Enzymatic hydrolysis. Half Life: 3 hours

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For treatment of central precocious puberty (true precocious puberty, GnRH-dependent precocious precocity, complete isosexual precocity) in children of both sexes and for the treatment of endometriosis.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

In experimental animals, a single subcutaneous administration of up to 60 times the recommended human dose (on a µg/kg basis, not adjusted for bioavailability) had no adverse effects. At present, there is no clinical evidence of adverse effects following overdosage of GnRH analogs.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB0014804

FooDB ID

Not Available

Phenol Explorer ID