Identification

Name
Gonadorelin
Accession Number
DB00644  (APRD01001)
Type
Small Molecule
Groups
Approved, Investigational, 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
  • GnRH
  • GnRH-I
  • Gonadoliberin I
  • Gonadorelin
  • Gonadorelin decapeptide
  • Gonadorelina
  • Gonadoréline
  • Gonadorelinum
  • Gonadotropin-releasing hormone
External IDs
Abbott 41070 / AY 24031 / Hoe 471 / RU 19847
Product Ingredients
IngredientUNIICASInChI Key
Gonadorelin acetate2RG1XQ1NYJ52699-48-6OOBWZCWPKJOGPF-UHFFFAOYSA-N
Gonadorelin diacetate tetrahydrateL8CRY8PWF2Not AvailableQZBIKDNLZRFYMZ-KYOBJPNESA-N
Gonadorelin hydrochloride3PFC574ITA51952-41-1CXLJLMYFZCNNQA-HBBGHHHDSA-N
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 Pharmaceuticals1994-12-31Not applicableCanada
Lutrepulse Pws 0.8mg/vialPowder, for solution0.8 mgIntravenous; SubcutaneousFerring Pharmaceuticals1994-12-31Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Relisorm 100 for Inj.-pws Liq-kit Sc IVGonadorelin (100 mcg) + Sodium Chloride (0.9 %)Liquid; Powder, for solutionIntravenous; SubcutaneousEmd Serono, A Division Of Emd Inc., Canada1994-12-31Not applicableCanada
Relisorm 500 for Inj.-pws Liq-kit IV ScGonadorelin (500 mcg) + Sodium Chloride (.9 %)Liquid; Powder, for solutionIntravenous; SubcutaneousEmd Serono, A Division Of Emd Inc., Canada1994-12-31Not applicableCanada
International/Other Brands
Fertagyl / Gonadorelin (Intrapharm) / HRF (Intrapharm) / Hypocrine (Tanabe Mitsubishi Pharma) / Kryptocur (Sanofi-Aventis) / Lutrelef (Ferring) / Relefact (Sanofi-Aventis)
Categories
UNII
9O7312W37G
CAS number
33515-09-2
Weight
Average: 1182.2901
Monoisotopic: 1181.573025571
Chemical Formula
C55H75N17O13
InChI Key
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

Pharmacology

Indication

For 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.

Associated Therapies
Pharmacodynamics

Gonadorelin 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 action

Systemic - 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.

TargetActionsOrganism
AGonadotropin-releasing hormone receptor
agonist
Human
APutative gonadotropin-releasing hormone II receptor
agonist
Human
Absorption

Rapidly absorbed when injected

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Rapidly hydrolyzed to inactive peptide components

Route of elimination
Not Available
Half life

Very short, initial, 2 to 10 minutes; terminal, 10 to 40 minutes

Clearance
Not Available
Toxicity

LD50>3000 mg/kg (rat, oral)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Capromab pendetideGonadorelin may decrease effectiveness of Capromab pendetide as a diagnostic agent.
Choline C 11Gonadorelin may decrease effectiveness of Choline C 11 as a diagnostic agent.
Conestat alfaThe risk or severity of thromboembolism can be increased when Gonadorelin is combined with Conestat alfa.
Corifollitropin alfaThe therapeutic efficacy of Corifollitropin alfa can be increased when used in combination with Gonadorelin.
Human C1-esterase inhibitorThe risk or severity of thromboembolism can be increased when Gonadorelin is combined with Human C1-esterase inhibitor.
Food Interactions
Not 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
Human Metabolome Database
HMDB0014782
KEGG Compound
C07607
PubChem Compound
36523
PubChem Substance
46506144
ChemSpider
33562
ChEMBL
CHEMBL1981292
Therapeutic Targets Database
DAP001052
PharmGKB
PA449801
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gonadorelin
ATC Codes
V04CM01 — GonadorelinH01CA01 — Gonadorelin
AHFS Codes
  • 68:18.00 — Gonadotropins
  • 36:66.00 — Pituitary Function
MSDS
Download (32 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingBasic ScienceSleep Restriction1
1RecruitingOtherGonadotrophin releasing hormone deficiency / Idiopathic hyperprolactinemic disorder / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia / Polycystic Ovarian Syndrome1
1RecruitingOtherGonadotrophin releasing hormone deficiency / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia / Puberty, Delayed1
1RecruitingOtherHealthy Postmenopausal Women / Hypergonadotropic Hypogonadism in Men / Idiopathic Hypogonadotropic Hypogonadism / Klinefelter's Syndrome / Primary Gonadal Insufficiency in Men1
1RecruitingPreventionIdiopathic Hypogonadotropic Hypogonadism1
2CompletedTreatmentHormonal Cycling / Malignancies / Prostate1
2CompletedTreatmentInfertilities1
2CompletedTreatmentProstate Cancer1
2RecruitingTreatmentAmenorrhea / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia1
2RecruitingTreatmentHypogonadism / Idiopathic hyperprolactinemic disorder1
2RecruitingTreatmentProstate Cancer1
2TerminatedTreatmentHypogonadism / Olfacto genital dysplasia1
2, 3Active Not RecruitingNot AvailableHealthy Volunteers / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia1
2, 3Active Not RecruitingOtherHealthy Volunteers1
2, 3CompletedTreatmentInfertilities1
3CompletedTreatmentPrimary Amenorrhea With Hypogonadotropic Hypogonadism1
3CompletedTreatmentProstate Cancer1
3RecruitingTreatmentProstatic Neoplasms1
4RecruitingTreatmentInfertilities1
4Unknown StatusDiagnosticCentral Precocious Puberty (CPP) / Sexual Precocity1
Not AvailableActive Not RecruitingBasic SciencePuberty, Precocious1
Not AvailableActive Not RecruitingTreatmentGonadotrophin releasing hormone deficiency / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia1
Not AvailableCompletedNot AvailableBMI >30 kg/m21
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Fertility1
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Infertilities1
Not AvailableCompletedHealth Services ResearchGonadal Disorders / Hypogonadism / Olfacto genital dysplasia1
Not AvailableCompletedTreatmentInfertilities1
Not AvailableRecruitingBasic ScienceBMI >30 kg/m2 / Hyperinsulinemia / Hypogonadotropic Hypogonadotropism / Infertilities1
Not AvailableRecruitingDiagnosticGonadotrophin releasing hormone deficiency / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia1
Not AvailableRecruitingTreatmentIdiopathic Hypogonadotropic Hypogonadism1

Pharmacoeconomics

Manufacturers
  • Ferring pharmaceuticals inc
  • Baxter healthcare corp anesthesia critical care
Packagers
  • Hospira Inc.
  • Intervet International
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
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound 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
Peptides / Tyrosine and derivatives / Phenylalanine and derivatives / Histidine and derivatives / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Proline and derivatives / Tryptamines and derivatives / Serine and derivatives / Alpha amino acid amides
show 23 more
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 / Triptan / Alpha-amino acid amide
show 48 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Gonadotropin-releasing hormone [KO:K05252] (C07607)

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...
Gene Name
GNRHR
Uniprot ID
P30968
Uniprot Name
Gonadotropin-releasing hormone receptor
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
Uniprot Name
Putative gonadotropin-releasing hormone II receptor
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]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 04:44