Identification

Name
Cetrorelix
Accession Number
DB00050  (BTD00115, APRD00686, BIOD00115)
Type
Small Molecule
Groups
Approved, 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 IDs
SB 75
Product Ingredients
IngredientUNIICASInChI Key
Cetrorelix AcetateXPQ226310Q145672-81-7KFEFLCOCAHJBEA-ANRVCLKPSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CetrotidePowder, for solution0.25 mgSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2004-03-03Not applicableCanada
CetrotideInjection, powder, for solution0.25 mgSubcutaneousMerck Serono Europe Limited1999-04-13Not applicableEu
CetrotidePowder, for solution3 mgSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2004-02-252014-10-20Canada
CetrotideKitSubcutaneousEmd Serono2000-08-11Not applicableUs
CetrotideInjection, powder, for solution0.25 mgSubcutaneousMerck Serono Europe Limited1999-04-13Not applicableEu
Categories
UNII
OON1HFZ4BA
CAS number
120287-85-6
Weight
Average: 1431.038
Monoisotopic: 1429.669818444
Chemical Formula
C70H92ClN17O14
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[[email protected]](NC(=O)[[email protected]@H](CCCNC(N)=O)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]](CO)NC(=O)[[email protected]@H](CC1=CN=CC=C1)NC(=O)[[email protected]@H](CC1=CC=C(Cl)C=C1)NC(=O)[[email protected]@H](CC1=CC2=CC=CC=C2C=C1)NC(C)=O)C(=O)N[[email protected]@H](CCCNC(N)=N)C(=O)N1CCC[[email protected]]1C(=O)N[[email protected]](C)C(N)=O

Pharmacology

Indication

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

Structured Indications
Not Available
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
ULutropin-choriogonadotropic hormone receptorNot AvailableHuman
AGonadotropin-releasing hormone receptor
antagonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14261
KEGG Drug
D01685
PubChem Compound
25074887
PubChem Substance
46505494
ChemSpider
10482082
BindingDB
50369965
ChEBI
59224
ChEMBL
CHEMBL1200490
Therapeutic Targets Database
DAP000096
PharmGKB
PA164764506
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cetrorelix
ATC Codes
H01CC02 — Cetrorelix
AHFS Codes
  • 92:40.00 — Gonadotropin-releasing Hormone Antagonists
FDA label
Download (221 KB)
MSDS
Download (35.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingBasic ScienceAging / Menopause1
0CompletedScreeningInfertilities1
1, 2WithdrawnNot AvailableAdministration of Increased Dose of GnRH Antagonist for Coasting for Decreasing the Risk for Ovarian Hyperstimulation Syndrome( OHSS)1
2CompletedTreatmentAssisted Reproduction1
2CompletedTreatmentEndometriosis1
2CompletedTreatmentRheumatoid Arthritis1
2RecruitingTreatmentInfertilities1
2TerminatedTreatmentInfertilities / Ovulation induction therapy1
2, 3Active Not RecruitingTreatmentInfertilities1
3CompletedTreatmentBenign Prostatic Hypertrophy (BPH)1
3CompletedTreatmentEffects of Gonadotropin / Oocyte Maturation / Ovarian Hyperstimulation Syndrome1
3CompletedTreatmentInfertilities / OHSS / Polycystic Ovarian Syndrome1
3CompletedTreatmentInfertilities / Polycystic Ovaries Syndrome1
3CompletedTreatmentOther Complications Associated With Artificial Fertilization1
3CompletedTreatmentPolycystic Ovarian Syndrome1
3TerminatedTreatmentBenign Prostatic Hypertrophy (BPH)1
3Unknown StatusScreeningEmbryo's Genetic and Chromosomal Quality1
4CompletedNot AvailableEffect of Two Protocols of Ovarian Stimulation on Oocyte Quality1
4CompletedNot AvailableLeiomyomas1
4CompletedTreatmentInfertile Women Undergoing Assisted Reproductive Technology (ART)1
4CompletedTreatmentInfertilities2
4CompletedTreatmentInvitro Fertilization1
4CompletedTreatmentSubfertility1
4RecruitingSupportive CareAssisted Reproductive Technology therapy / Infertilities1
4RecruitingTreatmentInfertilities1
4TerminatedTreatmentAssisted Reproductive Technology therapy / Intracytoplasmic Sperm Injection1
4Unknown StatusTreatmentAneuploidy / Blastocyst Disintegration / Chemical Pregnancy / Complication of Implant / Embryo/Fetus Death1
4Unknown StatusTreatmentPoor Responders Undergoing IVF1
Not AvailableCompletedNot AvailableBMI >30 kg/m21
Not AvailableCompletedNot AvailableInfertilities2
Not AvailableCompletedTreatmentFertility1
Not AvailableCompletedTreatmentInfertilities3
Not AvailableCompletedTreatmentPremenopause1
Not AvailableNot Yet RecruitingOtherEmbryonic Quality Using MitoScore (DuoStim x Conventional Stimulation Protocol) / Potential Usefulness of the DuoStim Protocol / Rate of Euploid Embryos Per Cycle (DuoStim x Conventional Stimulation Protocol)1
Not AvailableNot Yet RecruitingTreatmentOvarian Hyperstimulation Syndrome1
Not AvailableUnknown StatusTreatmentComplications Associated With Artificial Fertilization / Female Infertility Due to Nonimplantation of Ovum1
Not AvailableUnknown StatusTreatmentInfertilities1

Pharmacoeconomics

Manufacturers
  • Emd serono inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous0.25 mg
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)
US5198533No1993-10-242010-10-24Us
CA2115943No2003-08-052014-02-18Canada
US6319192No1999-04-232019-04-23Us

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)9.49ChemAxon
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 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

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 / 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
Polypeptide / Alpha peptide / Tyrosine or derivatives / Phenylalanine or derivatives / Leucine or derivatives / Proline or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Serine or derivatives / Alanine or derivatives
show 47 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oligopeptide (CHEBI:59224)

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
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. [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...
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. [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]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34