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Identification
Name Cetrorelix
Accession Number DB00050 (APRD00686, BIOD00115, BTD00115)
Type biotech
Groups approved
Description

Cetrorelix is a man-made hormone that blocks the effects of Gonadotropin Releasing Hormone (GnRH). GnRH controls another hormone that is called luteinizing hormone (LH), which is the hormone that starts ovulation during the menstrual cycle. When undergoing hormone treatment sometimes premature ovulation can occur, leading to eggs that are not ready for fertilization to be released. Cetrorelix does not allow the premature release of these eggs to occur.
Protein structure
Protein chemical formula C72H96ClN17O16
Protein average weight 1491.0900
Sequences
Synonyms
  • Cetrorelix Acetate
  • Cetrorelixum [INN-Latin]
  • SB 75
  • SB-75
Brand names
  • Cetrotide
Brand name mixtures Not Available
Categories
  • Infertility Agents
  • Hormone Antagonists
CAS number 120287-85-6
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the inhibition of premature LH surges in women undergoing controlled ovarian stimulation
Pharmacodynamics Cetrorelix is a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity. GnRH induces the production and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the gonadotrophic cells of the anterior pituitary. Due to a positive estradiol (E2) feedback at midcycle, GnRH liberation is enhanced resulting in an LH-surge. This LH-surge induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization as indicated by rising progesterone levels. Cetrorelix competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner.
Mechanism of action Cetrorelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion. It competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner.
Absorption Rapidly absorbed following subcutaneous injection. The mean absolute bioavailability following subcutaneous administration to healthy female subjects is 85%.
Volume of distribution
  • 1.16 L/kg
Protein binding 86%
Metabolism

In in vitro studies, cetrorelix was stable against phase I- and phase II-metabolism. Cetrorelix was transformed by peptidases, and the (1-4) peptide was the predominant metabolite.
Route of elimination Following subcutaneous administration of 10 mg cetrorelix to males and females, only unchanged cetrorelix was detected in urine.
Half life ~62.8 hours
Clearance
  • 1.28 ml/min·kg [adult healthy female with 3 mg single SC administration]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Emd serono inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Subcutaneous
Powder, for solution Subcutaneous 0.25 mg
Powder, for solution Subcutaneous 3 mg
Prices
Unit description Cost Unit
Cetrotide 3 mg kit 689.92 USD kit
Cetrotide 0.25 mg kit 137.99 USD kit
Patents
Country Patent Number Approved Expires
United States 6319192 1998-04-23 2018-04-23
United States 5198533 1993-10-24 2010-10-24
Canada 2115943 2003-08-05 2014-02-18
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PharmGKB PA10255 Link_out
Drug Product Database 2247767 Link_out
RxList http://www.rxlist.com/cgi/generic2/cetrorelix.htm Link_out
Drugs.com http://www.drugs.com/cdi/cetrorelix-acetate.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Cetrorelix Link_out
ATC Codes
  • H01CC02
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label show (221.2 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Gonadotropin-releasing hormone receptor

Pharmacological action: yes
Actions: antagonist

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. Volker P, Grundker C, Schmidt O, Schulz KD, Emons G: Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues. Am J Obstet Gynecol. 2002 Feb;186(2):171-9. Pubmed
  2. Zapatero-Caballero H, Sanchez-Franco F, Guerra-Perez N, Fernandez-Mendez C, Fernandez-Vazquez G: Gonadotropin-releasing hormone receptor gene expression during pubertal development of male rats. Biol Reprod. 2003 May;68(5):1764-70. Epub 2002 Dec 11. Pubmed
  3. Zapatero-Caballero H, Sanchez-Franco F, Fernandez-Mendez C, Garcia-San Frutos M, Botella-Cubells LM, Fernandez-Vazquez G: Gonadotropin-releasing hormone receptor gene expression during pubertal development of female rats. Biol Reprod. 2004 Feb;70(2):348-55. Epub 2003 Oct 15. Pubmed
  4. Roth C, Hegemann F, Hildebrandt J, Balzer I, Witt A, Wuttke W, Jarry H: Pituitary and gonadal effects of GnRH (gonadotropin releasing hormone) analogues in two peripubertal female rat models. Pediatr Res. 2004 Jan;55(1):126-33. Epub 2003 Nov 6. Pubmed
  5. Castellon E, Clementi M, Hitschfeld C, Sanchez C, Benitez D, Saenz L, Contreras H, Huidobro C: Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma. Cancer Invest. 2006 Apr-May;24(3):261-8. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Lutropin-choriogonadotropic hormone receptor

Pharmacological action: unknown

Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase

Organism class: human
UniProt ID: P22888 Link_out
Gene: LHCGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Ascoli M, Fanelli F, Segaloff DL: The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev. 2002 Apr;23(2):141-74. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on July 31, 2011 23:03

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.