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Identification
Name Gonadorelin
Accession Number DB00644 (APRD01001)
Type small molecule
Groups 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Dirigestran
Dirigestran Spofa
Factrel
Fertagyl
Gonadorelina [INN-Spanish]
Gonadorelinum [INN-Latin]
Gonadotropin releasing hormone
Gonadotropin-releasing factor
Gonadotropin-releasing hormone
Human LH-RH
Hypocrine
Luforan
Lutal
Lutamin
Lutrefact
Lutrepulse
Lutrepulse KIT
Mammalian GnRH
Mammalian LH-RH
Ovine LH-RH
Porchine LH-RH
Porcine LH-releasing factor
Relefact
Relisorm
Relisorm L
Synthetic decapeptide FSH/LH-RH
Synthetic Gn-RH
Synthetic gonadoliberin
Synthetic LH-FSH releasing hormone
Synthetic LH-releasing factor
Synthetic LH-releasing hormone
Synthetic LH-RF
Synthetic LH-RH
Synthetic LRF
First Prev Next Last
Brand mixtures Not Available
Categories
  • Fertility Agents, Female
CAS number 6918-09-8
Weight Average: 1182.2901
Monoisotopic: 1181.573025571
Chemical Formula C55H75N17O13
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Polypeptides
  • Tryptamines and Derivatives
  • Gamma Lactams
Substructures
  • Polypeptides
  • Hydroxy Compounds
  • Indoles and Indole Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Pyrroles
  • Pyrrolidines
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Tryptamines and Derivatives
  • Carbamates and Derivatives
  • Alcohols and Polyols
  • Imidazoles
  • Phenethylamines
  • Heterocyclic compounds
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Gamma Lactams
  • Lactams
  • Imines
  • Cyanamides
  • Phenyl Esters
  • Amphetamines
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.
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.
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
Pharmacoeconomics
Manufacturers
  • Ferring pharmaceuticals inc
  • Baxter healthcare corp anesthesia critical care
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
water solubility 1 mg/mL Not Available
logP -3.6 Not Available
Predicted Properties
Property Value Source
water solubility 5.88e-02 g/l ALOGPS
logP -0.09 ALOGPS
logP -6.3 ChemAxon
logS -4.3 ALOGPS
pKa (strongest acidic) 9.47 ChemAxon
pKa (strongest basic) 11.16 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 17 ChemAxon
hydrogen donor count 16 ChemAxon
polar surface area 474.63 ChemAxon
rotatable bond count 31 ChemAxon
refractivity 302.51 ChemAxon
polarizability 121.19 ChemAxon
References
Synthesis Reference Not Available
General Reference
  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
  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
External Links
Resource Link
KEGG Compound C07607 Link_out
PubChem Compound 36523 Link_out
PubChem Substance 46506144 Link_out
ChemSpider 33562 Link_out
Therapeutic Targets Database DAP001052 Link_out
PharmGKB PA449801 Link_out
Drug Product Database 573760 Link_out
RxList http://www.rxlist.com/cgi/generic2/gonadorelin.htm Link_out
Drugs.com http://www.drugs.com/cdi/gonadorelin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Gonadorelin Link_out
ATC Codes
  • H01CA01
  • V04CM01
AHFS Codes
  • 68:18.00
PDB Entries Not Available
FDA label Not Available
MSDS show (32 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Gonadotropin-releasing hormone receptor

Pharmacological action: yes
Actions: agonist

Receptor for gonadotropin releasing hormone (GnRH) that mediate the action of GnRH to stimulate the secretion of the gonadotropic hormones (LH and FSH). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act a an inhibitor of GnRH-R signaling

Organism class: human
UniProt ID: P30968 Link_out
Gene: GNRHR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Gonadotropin-releasing hormone II receptor

Pharmacological action: yes
Actions: agonist

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)

Organism class: human
UniProt ID: Q96P88 Link_out
Gene: GNRHR2 Link_out
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Marelli MM, 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
  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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19