Cetrorelix

Identification

Summary

Cetrorelix is a synthetic peptide antagonist of gonadotropin releasing hormone used to prevent luteinizing hormone surges in women undergoing assisted reproduction therapy.

Brand Names
Cetrotide
Generic Name
Cetrorelix
DrugBank Accession Number
DB00050
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 1431.038
Monoisotopic: 1429.669818444
Chemical Formula
C70H92ClN17O14
Synonyms
  • Cetrorelix
  • Cetrorelixum
External IDs
  • SB 75
  • SB-75

Pharmacology

Indication

For the inhibition of premature LH surges in women undergoing controlled ovarian stimulation

Pharmacology
Reduce drug development failure rates
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Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AGonadotropin-releasing hormone receptor
antagonist
Humans
ULutropin-choriogonadotropic hormone receptorNot AvailableHumans
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]
Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
No interactions found.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Cetrorelix acetateW9Y8L7GP4C130143-01-0DTPVYWHLQLAXFT-SMCUOGPFSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CetrotideInjection, powder, for solution0.25 mgSubcutaneousMerck Europe B.V.2016-09-08Not applicableEU flag
CetrotideKit3 mg/3mLSubcutaneousEMD Serono, Inc.2008-04-242008-04-24US flag
CetrotidePowder, for solution3 mg / vialSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2004-02-252014-10-20Canada flag
CetrotideInjection, powder, for solution0.25 mgSubcutaneousMerck Europe B.V.2016-09-08Not applicableEU flag
CetrotidePowder, for solution0.25 mg / vialSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2004-03-03Not applicableCanada flag
CetrotideKit0.25 mg/1mLSubcutaneousEMD Serono, Inc.2000-08-11Not applicableUS flag

Categories

ATC Codes
H01CC02 — Cetrorelix
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Proline and derivatives / Serine and derivatives / Alpha amino acid amides / Alanine and derivatives / Naphthalenes
show 24 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / Acetamide / Alanine or derivatives / Alcohol / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amphetamine or derivatives / Aromatic heteropolycyclic compound / Aryl chloride
show 47 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oligopeptide (CHEBI:59224)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
OON1HFZ4BA
CAS number
120287-85-6
InChI Key
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[C@H](NC(=O)[C@@H](CCCNC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](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[C@H]1C(=O)N[C@H](C)C(N)=O

References

General References
Not Available
Human Metabolome Database
HMDB0014261
KEGG Drug
D07665
PubChem Compound
25074887
PubChem Substance
46505494
ChemSpider
10482082
BindingDB
50369965
RxNav
68147
ChEBI
59224
ChEMBL
CHEMBL1200490
Therapeutic Targets Database
DAP000096
PharmGKB
PA164764506
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cetrorelix
FDA label
Download (221 KB)
MSDS
Download (35.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableEffect of Two Protocols of Ovarian Stimulation on Oocyte Quality1
4CompletedNot AvailableUterine Fibroids (Leiomyomas)1
4CompletedPreventionOvarian Hyper Stimulation Syndrome (OHSS)1
4CompletedTreatmentAssisted Reproduction1
4CompletedTreatmentFemale Infertility1
4CompletedTreatmentFertility / Optimal Stimulation Protocol / Reproductive Endocrinology1
4CompletedTreatmentIn Vitro Fertilization (IVF)1
4CompletedTreatmentInfertile Women Undergoing Assisted Reproductive Technology (ART)1
4CompletedTreatmentInfertility4
4CompletedTreatmentSubfertility1

Pharmacoeconomics

Manufacturers
  • Emd serono inc
Packagers
  • Baxter International Inc.
  • EMD Canada Inc.
  • Solvay Pharmaceuticals
Dosage Forms
FormRouteStrength
Injection, solution0.25 MG
Injection, powder, for solutionSubcutaneous
Injection, powder, for solutionSubcutaneous0.25 mg
KitSubcutaneous0.25 mg/1mL
KitSubcutaneous3 mg/3mL
Powder, for solutionSubcutaneous0.25 mg / vial
Powder, for solutionSubcutaneous3 mg / vial
Injection, powder, lyophilized, for solutionSubcutaneous
Injection
Injection, powder, lyophilized, for solutionSubcutaneous3 mg
Injection, powder, lyophilized, for solutionSubcutaneous0.25 mg
Powder0.25 mg/1vial
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)Region
US5198533No1993-03-302010-10-24US flag
CA2115943No2003-08-052014-02-18Canada flag
US6319192No2001-11-202019-04-23US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00694 mg/mLALOGPS
logP1.33ALOGPS
logP-1.7ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)9.5ChemAxon
pKa (Strongest Basic)11.79ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count18ChemAxon
Hydrogen Donor Count17ChemAxon
Polar Surface Area495.67 Å2ChemAxon
Rotatable Bond Count38ChemAxon
Refractivity384.16 m3·mol-1ChemAxon
Polarizability148.93 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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...
Gene Name
GNRHR
Uniprot ID
P30968
Uniprot Name
Gonadotropin-releasing hormone receptor
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Lutropin-choriogonadotropic hormone receptor
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. [Article]
  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. [Article]
  3. Ascoli M, Fanelli F, Segaloff DL: The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev. 2002 Apr;23(2):141-74. [Article]

Drug created on June 13, 2005 13:24 / Updated on September 18, 2021 03:34