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Identification
NameGonadorelin
Accession NumberDB00644  (APRD01001)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

Gonadorelin is another name for gonadotropin-releasing hormone (GnRH). It is a synthetic decapeptide prepared using solid phase peptide synthesis. GnRH is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pitutitary.

Structure
Thumb
Synonyms
Fertagyl
GnRH
GnRH-I
Gonadoliberin I
Gonadorelin
Gonadorelin decapeptide
Gonadorelina
Gonadoréline
Gonadorelinum
Gonadotropin-releasing hormone
External Identifiers
  • Abbott 41070
  • AY 24031
  • Hoe 471
  • RU 19847
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Factrel Inj 0.5mg/vialpowder for solution.5 mgintravenous; subcutaneousAyerst Laboratories1976-12-311996-09-10Canada
Factrel Pws 100mcg/vialpowder for solution100 mcgintravenous; subcutaneousWyeth Ayerst Canada Inc.1994-12-311999-10-26Canada
Factrel Pws 500mcg/vialpowder for solution500 mcgintravenous; subcutaneousWyeth Ayerst Canada Inc.1995-12-311999-10-26Canada
Lutrepulsepowder for solution3.2 mgintravenous; subcutaneousFerring Inc1994-12-31Not applicableCanada
Lutrepulse Pws 0.8mg/vialpowder for solution0.8 mgintravenous; subcutaneousFerring Inc1994-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
GonadorelinIntrapharm
HRFIntrapharm
HypocrineTanabe Mitsubishi Pharma
KryptocurSanofi-Aventis
LutrelefFerring
RelefactSanofi-Aventis
Brand mixtures
NameLabellerIngredients
Relisorm 100 for Inj.-pws Liq-kit Sc IVEmd Serono A Division Of Emd Inc Canada
Relisorm 500 for Inj.-pws Liq-kit IV ScEmd Serono A Division Of Emd Inc Canada
Salts
Name/CASStructureProperties
Gonadorelin acetate
52699-48-6
Thumb
  • InChI Key: OOBWZCWPKJOGPF-UHFFFAOYSA-N
  • Monoisotopic Mass: 1259.604719596
  • Average Mass: 1260.378
DBSALT001155
Gonadorelin diacetate tetrahydrate
ThumbNot applicableDBSALT000983
Gonadorelin hydrochloride
51952-41-1
Thumb
  • InChI Key: CXLJLMYFZCNNQA-HBBGHHHDSA-N
  • Monoisotopic Mass: 1217.5497033
  • Average Mass: 1218.77
DBSALT000982
Categories
UNII9O7312W37G
CAS number33515-09-2
WeightAverage: 1182.2901
Monoisotopic: 1181.573025571
Chemical FormulaC55H75N17O13
InChI KeyInChIKey=XLXSAKCOAKORKW-UHFFFAOYSA-N
InChI
InChI=1S/C55H75N17O13/c1-29(2)19-38(49(80)67-37(9-5-17-60-55(57)58)54(85)72-18-6-10-43(72)53(84)62-25-44(56)75)66-46(77)26-63-47(78)39(20-30-11-13-33(74)14-12-30)68-52(83)42(27-73)71-50(81)40(21-31-23-61-35-8-4-3-7-34(31)35)69-51(82)41(22-32-24-59-28-64-32)70-48(79)36-15-16-45(76)65-36/h3-4,7-8,11-14,23-24,28-29,36-43,61,73-74H,5-6,9-10,15-22,25-27H2,1-2H3,(H2,56,75)(H,59,64)(H,62,84)(H,63,78)(H,65,76)(H,66,77)(H,67,80)(H,68,83)(H,69,82)(H,70,79)(H,71,81)(H4,57,58,60)
IUPAC Name
N-(1-{2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl}-5-[(diaminomethylidene)amino]-1-oxopentan-2-yl)-2-{2-[2-(3-hydroxy-2-{2-[3-(1H-imidazol-5-yl)-2-[(5-oxopyrrolidin-2-yl)formamido]propanamido]-3-(1H-indol-3-yl)propanamido}propanamido)-3-(4-hydroxyphenyl)propanamido]acetamido}-4-methylpentanamide
SMILES
CC(C)CC(NC(=O)CNC(=O)C(CC1=CC=C(O)C=C1)NC(=O)C(CO)NC(=O)C(CC1=CNC2=CC=CC=C12)NC(=O)C(CC1=CN=CN1)NC(=O)C1CCC(=O)N1)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(=O)NCC(N)=O
Taxonomy
DescriptionThis compound 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
  • N-acyl-alpha amino acid or derivatives
  • Triptan
  • Alpha-amino acid amide
  • Phenylpropylamine
  • Amphetamine or derivatives
  • N-substituted-alpha-amino acid
  • Indole or derivatives
  • Indole
  • Pyrrolidine-2-carboxamide
  • Pyrrolidine carboxylic acid or derivatives
  • N-acylpyrrolidine
  • Phenol
  • Fatty acyl
  • Benzenoid
  • Substituted pyrrole
  • 2-pyrrolidone
  • Pyrrolidone
  • N-acyl-amine
  • Fatty amide
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Pyrrole
  • Imidazole
  • Azole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Primary carboxylic acid amide
  • Lactam
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
  • Gonadotropin-releasing hormone [KO:K05252] (C07607 )
Pharmacology
IndicationFor evaluating the functional capacity and response of the gonadotropes of the anterior pituitary also for evaluating residual gonadotropic function of the pituitary following removal of a pituitary tumor by surgery and/or irradiation.
PharmacodynamicsGonadorelin is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pitutitary. In the pituitary GnRH stimulates synthesis and release of FSH and LH, a process that is controlled by the frequency and amplitude of GnRH pulses, as well as the feedback of androgens and estrogens. The pulsatility of GnRH secretion has been seen in all vertebrates, and it is necessary to ensure a correct reproductive function. Thus a single hormone, GnRH, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male. Its short half life requires infusion pumps for its clinical use
Mechanism of actionSystemic - Like naturally occurring gonadotropin-releasing hormone (GnRH), gonadorelin primarily stimulates the synthesis and release of luteinizing hormone (LH) from the anterior pituitary gland. Follicle-stimulating hormone (FSH) production and release is also increased by gonadorelin, but to a lesser degree. In prepubertal females and some gonadal function disorders, the FSH response may be greater than the LH response. For the treatment of amenorrhea, delayed puberty, and infertility the administration of gonadorelin is used to simulate the physiologic release of GnRH from the hypothalamus in treatment of delayed puberty, treatment of infertility caused by hypogonadotropic hypogonadism, and induction of ovulation in those women with hypothalamic amenorrhea. This results in increased levels of pituitary gonadotropins LH and FSH, which subsequently stimulate the gonads to produce reproductive steroids.
Related Articles
AbsorptionRapidly absorbed when injected
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Rapidly hydrolyzed to inactive peptide components

Route of eliminationNot Available
Half lifeVery short, initial, 2 to 10 minutes; terminal, 10 to 40 minutes
ClearanceNot Available
ToxicityLD50>3000 mg/kg (rat, oral)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9695
Blood Brain Barrier-0.9781
Caco-2 permeable-0.8941
P-glycoprotein substrateSubstrate0.8607
P-glycoprotein inhibitor INon-inhibitor0.8452
P-glycoprotein inhibitor IINon-inhibitor0.7859
Renal organic cation transporterNon-inhibitor0.6797
CYP450 2C9 substrateNon-substrate0.769
CYP450 2D6 substrateNon-substrate0.7647
CYP450 3A4 substrateSubstrate0.5996
CYP450 1A2 substrateNon-inhibitor0.842
CYP450 2C9 inhibitorNon-inhibitor0.8493
CYP450 2D6 inhibitorNon-inhibitor0.9054
CYP450 2C19 inhibitorNon-inhibitor0.8136
CYP450 3A4 inhibitorNon-inhibitor0.7529
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9411
Ames testNon AMES toxic0.6992
CarcinogenicityNon-carcinogens0.7961
BiodegradationNot ready biodegradable0.9933
Rat acute toxicity2.6799 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9038
hERG inhibition (predictor II)Non-inhibitor0.5274
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Ferring pharmaceuticals inc
  • Baxter healthcare corp anesthesia critical care
Packagers
Dosage forms
FormRouteStrength
Powder for solutionintravenous; subcutaneous.5 mg
Powder for solutionintravenous; subcutaneous100 mcg
Powder for solutionintravenous; subcutaneous500 mcg
Powder for solutionintravenous; subcutaneous3.2 mg
Powder for solutionintravenous; subcutaneous0.8 mg
Liquid; powder for solutionintravenous; subcutaneous
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
water solubility1 mg/mLNot Available
logP-3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0588 mg/mLALOGPS
logP-0.09ALOGPS
logP-6.3ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.47ChemAxon
pKa (Strongest Basic)11.16ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area474.63 Å2ChemAxon
Rotatable Bond Count31ChemAxon
Refractivity302.51 m3·mol-1ChemAxon
Polarizability121.19 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Rainer Uhmann, Kurt Radscheit, “Process for the low-racemization preparation of peptide intermediates of the synthesis of gonadorelin and gonadorelin analogs, and new intermediates for this process.” U.S. Patent US4691008, issued December, 1984.

US4691008
General References
  1. Dungan HM, Clifton DK, Steiner RA: Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion. Endocrinology. 2006 Mar;147(3):1154-8. Epub 2005 Dec 22. [PubMed:16373418 ]
  2. Franceschini I, Lomet D, Cateau M, Delsol G, Tillet Y, Caraty A: Kisspeptin immunoreactive cells of the ovine preoptic area and arcuate nucleus co-express estrogen receptor alpha. Neurosci Lett. 2006 Jul 3;401(3):225-30. Epub 2006 Apr 18. [PubMed:16621281 ]
External Links
ATC CodesV04CM01H01CA01
AHFS Codes
  • 68:18.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (32 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Peptide binding
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:
37730.355 Da
References
  1. Lu ZL, Gallagher R, Sellar R, Coetsee M, Millar RP: Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor-binding sites specifically increase binding affinity for GnRH II but not GnRH I: evidence for ligand-selective, receptor-active conformations. J Biol Chem. 2005 Aug 19;280(33):29796-803. Epub 2005 Jun 20. [PubMed:15967801 ]
  2. Moles G, Carrillo M, Mananos E, Mylonas CC, Zanuy S: Temporal profile of brain and pituitary GnRHs, GnRH-R and gonadotropin mRNA expression and content during early development in European sea bass (Dicentrarchus labrax L.). Gen Comp Endocrinol. 2007 Jan 1;150(1):75-86. Epub 2006 Sep 8. [PubMed:16962597 ]
  3. Mamputha S, Lu ZL, Roeske RW, Millar RP, Katz AA, Flanagan CA: Conserved amino acid residues that are important for ligand binding in the type I gonadotropin-releasing hormone (GnRH) receptor are required for high potency of GnRH II at the type II GnRH receptor. Mol Endocrinol. 2007 Jan;21(1):281-92. Epub 2006 Sep 14. [PubMed:16973761 ]
  4. Lee PA, Houk CP: Gonadotropin-releasing hormone analog therapy for central precocious puberty and other childhood disorders affecting growth and puberty. Treat Endocrinol. 2006;5(5):287-96. [PubMed:17002488 ]
  5. Bliss SP, Navratil AM, Breed M, Skinner DC, Clay CM, Roberson MS: Signaling complexes associated with the type I gonadotropin-releasing hormone (GnRH) receptor: colocalization of extracellularly regulated kinase 2 and GnRH receptor within membrane rafts. Mol Endocrinol. 2007 Feb;21(2):538-49. Epub 2006 Oct 26. [PubMed:17068198 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Gonadotropin-releasing hormone receptor activity
Specific Function:
Putative receptor for gonadotropin releasing hormone II (GnRH II) which is most probably non-functional.
Gene Name:
GNRHR2
Uniprot ID:
Q96P88
Molecular Weight:
32536.935 Da
References
  1. Morgan K, Sellar R, Pawson AJ, Lu ZL, Millar RP: Bovine and ovine gonadotropin-releasing hormone (GnRH)-II ligand precursors and type II GnRH receptor genes are functionally inactivated. Endocrinology. 2006 Nov;147(11):5041-51. Epub 2006 Aug 17. [PubMed:16916952 ]
  2. Mamputha S, Lu ZL, Roeske RW, Millar RP, Katz AA, Flanagan CA: Conserved amino acid residues that are important for ligand binding in the type I gonadotropin-releasing hormone (GnRH) receptor are required for high potency of GnRH II at the type II GnRH receptor. Mol Endocrinol. 2007 Jan;21(1):281-92. Epub 2006 Sep 14. [PubMed:16973761 ]
  3. Montagnani Marelli M, Moretti RM, Januszkiewicz-Caulier J, Motta M, Limonta P: Gonadotropin-releasing hormone (GnRH) receptors in tumors: a new rationale for the therapeutical application of GnRH analogs in cancer patients? Curr Cancer Drug Targets. 2006 May;6(3):257-69. [PubMed:16712461 ]
  4. Li JH, Choe H, Wang AF, Maiti K, Wang C, Salam A, Chun SY, Lee WK, Kim K, Kwon HB, Seong JY: Extracellular loop 3 (EL3) and EL3-proximal transmembrane helix 7 of the mammalian type I and type II gonadotropin-releasing hormone (GnRH) receptors determine differential ligand selectivity to GnRH-I and GnRH-II. Mol Pharmacol. 2005 Apr;67(4):1099-110. Epub 2005 Jan 5. [PubMed:15635044 ]
  5. Silver MR, Sower SA: Functional characterization and kinetic studies of an ancestral lamprey GnRH-III selective type II GnRH receptor from the sea lamprey, Petromyzon marinus. J Mol Endocrinol. 2006 Jun;36(3):601-10. [PubMed:16720727 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23