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Identification
NameCetrorelix
Accession NumberDB00050  (BTD00115, APRD00686, BIOD00115)
TypeSmall Molecule
GroupsApproved, Investigational
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.

Structure
Thumb
Synonyms
Cetrorelixum
External Identifiers
  • SB 75
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CetrotidekitsubcutaneousEMD Serono, Inc.2000-08-11Not applicableUs
Cetrotidepowder for solution3 mgsubcutaneousEmd Serono A Division Of Emd Inc Canada2004-02-252014-10-20Canada
Cetrotidepowder for solution0.25 mgsubcutaneousEmd Serono A Division Of Emd Inc Canada2004-03-03Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Cetrorelix Acetate
145672-81-7
Thumb
  • InChI Key: KFEFLCOCAHJBEA-ANRVCLKPSA-N
  • Monoisotopic Mass: 1489.690947816
  • Average Mass: 1491.09
DBSALT000021
Categories
UNIIOON1HFZ4BA
CAS number120287-85-6
WeightAverage: 1431.038
Monoisotopic: 1429.669818444
Chemical FormulaC70H92ClN17O14
InChI KeyInChIKey=SBNPWPIBESPSIF-MHWMIDJBSA-N
InChI
InChI=1S/C70H92ClN17O14/c1-39(2)31-52(61(94)82-51(15-9-28-77-69(73)74)68(101)88-30-10-16-58(88)67(100)79-40(3)59(72)92)83-60(93)50(14-8-29-78-70(75)102)81-63(96)54(34-43-20-25-49(91)26-21-43)86-66(99)57(38-89)87-65(98)56(36-45-11-7-27-76-37-45)85-64(97)55(33-42-18-23-48(71)24-19-42)84-62(95)53(80-41(4)90)35-44-17-22-46-12-5-6-13-47(46)32-44/h5-7,11-13,17-27,32,37,39-40,50-58,89,91H,8-10,14-16,28-31,33-36,38H2,1-4H3,(H2,72,92)(H,79,100)(H,80,90)(H,81,96)(H,82,94)(H,83,93)(H,84,95)(H,85,97)(H,86,99)(H,87,98)(H4,73,74,77)(H3,75,78,102)/t40-,50-,51+,52+,53-,54+,55-,56-,57+,58+/m1/s1
IUPAC Name
(2S)-N-[(2S)-5-carbamimidamido-1-[(2S)-2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl]-1-oxopentan-2-yl]-2-[(2R)-5-(carbamoylamino)-2-[(2S)-2-[(2S)-2-[(2R)-2-[(2R)-3-(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-hydroxypropanamido]-3-(4-hydroxyphenyl)propanamido]pentanamido]-4-methylpentanamide
SMILES
CC(C)C[[email protected]](NC(=O)[C@@H](CCCNC(N)=O)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]](CO)NC(=O)[C@@H](CC1=CN=CC=C1)NC(=O)[C@@H](CC1=CC=C(Cl)C=C1)NC(=O)[C@@H](CC1=CC2=CC=CC=C2C=C1)NC(C)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[[email protected]]1C(=O)N[[email protected]](C)C(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
  • Alpha-amino acid amide
  • Phenylpropylamine
  • Naphthalene
  • Amphetamine or derivatives
  • N-substituted-alpha-amino acid
  • Pyrrolidine-2-carboxamide
  • Pyrrolidine carboxylic acid or derivatives
  • N-acylpyrrolidine
  • Phenol
  • Halobenzene
  • Chlorobenzene
  • Fatty acyl
  • Benzenoid
  • Pyridine
  • N-acyl-amine
  • Fatty amide
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Acetamide
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Urea
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Primary carboxylic acid amide
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboximidamide
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Imine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the inhibition of premature LH surges in women undergoing controlled ovarian stimulation
PharmacodynamicsCetrorelix 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 actionCetrorelix 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.
Related Articles
AbsorptionRapidly 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 binding86%
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 eliminationFollowing 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]
ToxicityNot Available
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+0.913
Blood Brain Barrier-0.9647
Caco-2 permeable-0.748
P-glycoprotein substrateSubstrate0.8796
P-glycoprotein inhibitor INon-inhibitor0.8235
P-glycoprotein inhibitor IIInhibitor0.6194
Renal organic cation transporterNon-inhibitor0.6856
CYP450 2C9 substrateNon-substrate0.7609
CYP450 2D6 substrateNon-substrate0.7938
CYP450 3A4 substrateSubstrate0.6358
CYP450 1A2 substrateNon-inhibitor0.7491
CYP450 2C9 inhibitorNon-inhibitor0.6987
CYP450 2D6 inhibitorNon-inhibitor0.8339
CYP450 2C19 inhibitorNon-inhibitor0.7056
CYP450 3A4 inhibitorInhibitor0.6531
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9001
Ames testNon AMES toxic0.6327
CarcinogenicityNon-carcinogens0.7553
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7014 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7601
hERG inhibition (predictor II)Inhibitor0.649
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Emd serono inc
Packagers
Dosage forms
FormRouteStrength
Kitsubcutaneous
Powder for solutionsubcutaneous0.25 mg
Powder for solutionsubcutaneous3 mg
Prices
Unit descriptionCostUnit
Cetrotide 3 mg kit689.92USD kit
Cetrotide 0.25 mg kit137.99USD kit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2115943 No2003-08-052014-02-18Canada
US5198533 No1993-10-242010-10-24Us
US6319192 No1999-04-232019-04-23Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00694 mg/mLALOGPS
logP1.33ALOGPS
logP-1.7ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)9.49ChemAxon
pKa (Strongest Basic)11.11ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count18ChemAxon
Hydrogen Donor Count17ChemAxon
Polar Surface Area495.67 Å2ChemAxon
Rotatable Bond Count38ChemAxon
Refractivity384.16 m3·mol-1ChemAxon
Polarizability148.09 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 ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesH01CC02
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (221 KB)
MSDSDownload (35.2 KB)
Interactions
Drug Interactions
Drug
CapromabCetrorelix may decrease effectiveness of Capromab as a diagnostic agent.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Luteinizing hormone receptor activity
Specific Function:
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Gene Name:
LHCGR
Uniprot ID:
P22888
Molecular Weight:
78642.01 Da
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:17139284 ]
  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:17016423 ]
  3. Ascoli M, Fanelli F, Segaloff DL: The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev. 2002 Apr;23(2):141-74. [PubMed:11943741 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
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. 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:11854630 ]
  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:12606421 ]
  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:14561652 ]
  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:14605254 ]
  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:16809153 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on August 24, 2016 01:51