Nafarelin (CED0009905)

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:23 UTC

Update Date

2026-05-14 16:45:32 UTC

Accession Number

CHEM002243

Identification

Common Name

Nafarelin

Class

Small Molecule

Description

Nafarelin is an exogenous solid with the formula C66H83N17O13. Nafarelin belongs to the polypeptides, a class of organic polymers within the organic compounds. With an average molecular weight of 1,322 g/mol, Nafarelin is a heavy molecule. It is sourced from healthcare, pharmaceuticals, and veterinary products as a hypothalamic hormone and is administered via the nasal route. The compound targets the gonadotropin-releasing hormone receptor (GNRHR) and the putative gonadotropin-releasing hormone II receptor (GNRHR2). Similar to GnRH, initial or intermittent administration of nafarelin stimulates the pituitary gland to release the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which transiently increases testosterone in both sexes and estradiol in females. Conversely, continuous daily administration results in the continuous occupation of the GnRH receptor, leading to a desensitization of the pituitary gonadotropes and a reversible down-regulation of the GnRH receptors in the pituitary gland.

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

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Organoleptic Effects

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	No	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	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00dr-9037302120-f0facb1967d30439597d	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00di-9011200000-e32adcd953ac1c721212	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00e9-9011100000-0e896538a04b95abd857	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0ukc-2194100000-e5cb37d2eafc7e73ef96	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-11b9-6595010100-3cfda325f415bde10f61	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-052f-9410011130-eb97257a1937988394bc	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0kg9-0017900031-0ad2341a5a6f67386398	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0abd-1133910111-a355010b703bbfdcb57f	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0pbl-1611920110-b8ca31d70aed9fbf9a0e	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00dl-1109300000-0c7604e46e8e28bdf55f	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0fkl-3829202140-80a733fe94b1819e25e8	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0096-5911304005-08b37dbd696b4e3af318	Not Available	View Spectrum
1D NMR	¹H NMR Spectrum (1D, D₂O, predicted)	Not Available	Not Available	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, D₂O, predicted)	Not Available	Not Available	View Spectrum

Toxicity Profile

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.

Carcinogenicity (IARC Classification)

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

Minimum Risk Level

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

Toxicity Values

Not Available

Health Effects

Health Effect	Relationship	Direction	Reference

Exposure Sources

Source ID	Source	Sector	Reference
330	Hypothalamic hormones	Healthcare, pharmaceuticals & veterinary products	Not Available

Pathways

1 pathway

Nafarelin Drug Metabolism Action Pathway

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	Neuromedin-U receptor 2	Q8BZ39	Mus musculus	Predicted (SEA)	4.67095
Click to view 3D structure	Prolactin-releasing peptide	P81277	Humans	Predicted (SEA)	20.0851
Click to view 3D structure	Melanocortin receptor 4	P32245	Humans	Predicted (SEA)	30.5169
Click to view 3D structure	Glucagon-1	O42143	Xenopus laevis	Predicted (SEA)	24.2111
Click to view 3D structure	Melanocyte-stimulating hormone receptor	Q01726	Humans	Predicted (SEA)	22.6541
Click to view 3D structure	Kappa-type opioid receptor	P41144	Cavia porcellus	Predicted (SEA)	62.5908
Click to view 3D structure	Mu-type opioid receptor	P97266	Cavia porcellus	Predicted (SEA)	70.6092
Click to view 3D structure	Melanocortin receptor 5	P33032	Humans	Predicted (SEA)	22.187
Click to view 3D structure	Kappa-type opioid receptor	P41145	Humans	Predicted (SEA)	81.9752
Click to view 3D structure	Delta-type opioid receptor	P41143	Humans	Predicted (SEA)	92.407
Click to view 3D structure	Melanocortin receptor 3	P33033	Mus musculus	Predicted (SEA)	19.4623
Click to view 3D structure	Neuromedin-U receptor 1	O55040	Mus musculus	Predicted (SEA)	11.8331
Click to view 3D structure	Melanocortin receptor 3	P41968	Humans	Predicted (SEA)	24.3668
Click to view 3D structure	Mu-type opioid receptor	P35372	Humans	Predicted (SEA)	88.7481
Click to view 3D structure	Mu-type opioid receptor	P33535	Rattus norvegicus	Predicted (SEA)	84.155
Click to view 3D structure	Melanocyte-stimulating hormone receptor	Q01727	Mus musculus	Predicted (SEA)	28.1036
Click to view 3D structure	Delta-type opioid receptor	P33533	Rattus norvegicus	Predicted (SEA)	59.6325
Click to view 3D structure	Melanocortin receptor 5	P41149	Mus musculus	Predicted (SEA)	28.1036
Click to view 3D structure	Dickkopf WNT-signaling pathway inhibitor 1	A6I0Z0	Rattus norvegicus	Predicted (SEA)	37.679
Click to view 3D structure	Delta-type opioid receptor	P32300	Mus musculus	Predicted (SEA)	78.3942
Click to view 3D structure	Neuropeptide FF receptor 2	Q9Y5X5	Humans	Predicted (SEA)	37.2898
Click to view 3D structure	Melanocortin receptor 4	P56450	Mus musculus	Predicted (SEA)	28.0257
Click to view 3D structure	G-protein coupled receptor Mth	O97148	Drosophila melanogaster	Predicted (SEA)	33.6309
Click to view 3D structure	Neuropeptide FF receptor 1	Q9GZQ6	Humans	Predicted (SEA)	31.9182
Click to view 3D structure	Substance-P receptor	P25103	Humans	Predicted (SEA)	30.5947
Click to view 3D structure	Gonadotropin-releasing hormone receptor	P30968	Humans	Known	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. A reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes occur. 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. Nafarelin does not abolish the underlying pathophysiology of endometriosis, however.
Click to view 3D structure	Putative gonadotropin-releasing hormone II receptor	Q96P88	Humans	Known	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. A reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes occur. 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. Nafarelin does not abolish the underlying pathophysiology of endometriosis, however.