Identification

Name
Ganirelix
Accession Number
DB06785
Type
Small Molecule
Groups
Approved
Description

Ganirelix is an injectable competitive gonadotropin-releasing hormone antagonist (GnRH antagonist). It is primarily used in assisted reproduction to control ovulation. The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of LH and FSH. Ganirelix is used in fertility treatment to prevent premature ovulation that could result in the harvesting of eggs that are too immature to be used in procedures such as in vitro fertilisation. Ganirelix is marketed by Merck & Co., Inc. as Orgalutran®.

Structure
Thumb
Synonyms
Not Available
External IDs
Org 37462 / RS 26306 / SML0241
Product Ingredients
IngredientUNIICASInChI Key
Ganirelix acetate56U7906FQW129311-55-3OVBICQMTCPFEBS-SATRDZAXSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ganirelix AcetateInjection, solution250 ug/0.5mLSubcutaneousOrganon1999-07-29Not applicableUs
OrgalutranSolution250 mcgSubcutaneousMerck Ltd.2002-08-23Not applicableCanada
OrgalutranInjection, solution0.25 mg/0.5mLSubcutaneousMerck Sharp & Dohme Limited2000-05-17Not applicableEu
OrgalutranInjection, solution0.25 mg/0.5mLSubcutaneousMerck Sharp & Dohme Limited2000-05-17Not applicableEu
Categories
UNII
IX503L9WN0
CAS number
124904-93-4
Weight
Average: 1570.35
Monoisotopic: 1568.8423035
Chemical Formula
C80H113ClN18O13
InChI Key
GJNXBNATEDXMAK-PFLSVRRQSA-N
InChI
InChI=1S/C80H113ClN18O13/c1-9-84-79(85-10-2)88-38-17-15-24-60(70(104)94-62(41-49(5)6)71(105)93-61(25-16-18-39-89-80(86-11-3)87-12-4)78(112)99-40-20-26-68(99)77(111)90-50(7)69(82)103)92-73(107)64(44-53-30-35-59(102)36-31-53)97-76(110)67(48-100)98-75(109)66(46-55-21-19-37-83-47-55)96-74(108)65(43-52-28-33-58(81)34-29-52)95-72(106)63(91-51(8)101)45-54-27-32-56-22-13-14-23-57(56)42-54/h13-14,19,21-23,27-37,42,47,49-50,60-68,100,102H,9-12,15-18,20,24-26,38-41,43-46,48H2,1-8H3,(H2,82,103)(H,90,111)(H,91,101)(H,92,107)(H,93,105)(H,94,104)(H,95,106)(H,96,108)(H,97,110)(H,98,109)(H2,84,85,88)(H2,86,87,89)/t50-,60-,61+,62+,63-,64+,65-,66-,67+,68+/m1/s1
IUPAC Name
(2R)-6-{[bis(ethylamino)methylidene]amino}-N-[(1S)-1-{[(2S)-6-{[bis(ethylamino)methylidene]amino}-1-[(2S)-2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl]-1-oxohexan-2-yl]carbamoyl}-3-methylbutyl]-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]hexanamide
SMILES
CCNC(NCC)=NCCCC[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC1=CC=CN=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](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O

Pharmacology

Indication

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

Associated Therapies
Pharmacodynamics
Not Available
Mechanism of action

Ganirelix acts by competitively blocking the GnRH receptors on the pituitary gonadotroph and subsequent transduction pathway. It induces a rapid, reversible suppression of gonadotropin secretion. The suppression of pituitary LH secretion by ganirelix is more pronounced than that of FSH. An initial release of endogenous gonadotropins has not been detected with ganirelix, which is consistent with an antagonist effect. Upon discontinuation of ganirelix, pituitary LH and FSH levels are fully recovered within 48 hours.

TargetActionsOrganism
AGonadotropin-releasing hormone receptor
antagonist
Human
Absorption

Ganirelix is rapidly absorbed following subcutaneous injection with maximum serum concentrations reached approximately one hour after dosing.

Volume of distribution

The mean (SD) volume of distribution of Ganirelix in healthy females following intravenous administration of a single 250 mg dose is 43.7 (11.4) L.

Protein binding

81.9%.

Metabolism

Following single-dose intravenous administration of radiolabeled ganirelix acetate to healthy female volunteers, ganirelix Acetate is the major compound present in the plasma (50–70% of total radioactivity in the plasma) up to 4 hours and urine (17.1–18.4% of administered dose) up to 24 hours. Ganirelix Acetate is not found in the feces. The 1–4 peptide and 1–6 peptide of Ganirelix Acetate are the primary metabolites observed in the feces.

Route of elimination

On average, 97.2% of the total radiolabeled ganirelix dose is recovered in the feces and urine (75.1% and 22.1%, respectively) over 288 h following intravenous single dose administration of 1 mg [14 75 C]-ganirelix acetate. Urinary excretion is virtually complete in 24 h, whereas fecal excretion starts to plateau 192 h after dosing.

Half life

16.2 hours.

Clearance

Single dose: 2.4L/hour Multiple dose: 3.3L/hour

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

"Patent Link":http://www.google.ca/patents/US5767082

General References
  1. Oberye J, Mannaerts B, Huisman J, Timmer C: Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections. Hum Reprod. 2000 Feb;15(2):245-9. [PubMed:10655292]
  2. Royster GD, Retzloff MG, Robinson RD, King JA, Propst AM: Effect of length of controlled ovarian hyperstimulation using a gonadotropin-releasing hormone antagonist on in vitro fertilization pregnancy rates. J Reprod Med. 2012 Sep-Oct;57(9-10):415-20. [PubMed:23091989]
External Links
KEGG Drug
D08010
PubChem Compound
16130957
PubChem Substance
310264884
ChemSpider
17287671
BindingDB
50102454
ChEBI
135910
ChEMBL
CHEMBL1251
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ganirelix
ATC Codes
H01CC01 — Ganirelix
AHFS Codes
  • 92:40.00 — Gonadotropin-releasing Hormone Antagonists
FDA label
Download (62.6 KB)
MSDS
Download (60.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic SciencePolycystic Ovaries Syndrome1
0CompletedBasic SciencePuberty, Delayed / Puberty, Precocious1
1RecruitingBasic ScienceSleep Restriction1
1, 2CompletedTreatmentOvarian Stimulation1
2CompletedBasic ScienceOrthostatic Intolerance1
2CompletedTreatmentAssisted Reproductive Technology therapy / Infertilities1
2CompletedTreatmentControlled Ovarian Stimulation1
3CompletedTreatmentAssisted Reproductive Technology therapy1
3CompletedTreatmentControlled Ovarian Stimulation1
3CompletedTreatmentInfertilities / Poor Ovarian Response1
3RecruitingPreventionInfertilities1
3Unknown StatusScreeningEmbryo's Genetic and Chromosomal Quality1
3Unknown StatusTreatmentInfertilities1
3WithdrawnTreatmentInfertilities1
4CompletedNot AvailableInfertilities / Premature Ovarian Failure (POF)1
4CompletedOtherInfertilities1
4CompletedTreatmentEgg Donation1
4CompletedTreatmentInfertilities / IVF Treatment1
4CompletedTreatmentInfertile Women Undergoing Assisted Reproductive Technology (ART)1
4CompletedTreatmentInfertilities2
4CompletedTreatmentInfertilities / Premature Ovarian Failure (POF)1
4RecruitingTreatmentControlled Ovarian Stimulation1
4TerminatedTreatmentAssisted Reproductive Technology therapy1
4TerminatedTreatmentAssisted Reproductive Technology therapy / Ovulation induction therapy1
4Unknown StatusPreventionOvarian Hyperstimulation Syndrome / Polycystic Ovaries Syndrome1
4Unknown StatusTreatmentInfertilities1
Not AvailableActive Not RecruitingBasic ScienceAging / Arterial Stiffening / Menopause1
Not AvailableCompletedNot AvailableAssisted Reproductive Technology therapy1
Not AvailableCompletedNot AvailableFertilization in Vitro1
Not AvailableCompletedNot AvailableImplantation, Embryo / Pregnancy1
Not AvailableCompletedNot AvailableInfertilities1
Not AvailableCompletedNot AvailableInfertility, Subfertility1
Not AvailableCompletedNot AvailableNeonates / Pregnancy2
Not AvailableCompletedTreatmentCompare Pregnancy Rates Between FSH Stimulation and FSH and / GnRH Antagonist1
Not AvailableCompletedTreatmentFertility1
Not AvailableCompletedTreatmentFertility Preservation / Infertilities / Oocyte Donation / Ovulation induction therapy / Vitrification1
Not AvailableNot Yet RecruitingTreatmentEndometriosis1
Not AvailableNot Yet RecruitingTreatmentInfertilities1
Not AvailableRecruitingOtherEmbryonic Quality Using MitoScore (DuoStim x Conventional Stimulation Protocol) / Infertility, Female / Potential Usefulness of the DuoStim Protocol / Rate of Euploid Embryos Per Cycle (DuoStim x Conventional Stimulation Protocol)1
Not AvailableRecruitingTreatmentInfertilities1
Not AvailableTerminatedTreatmentAssisted Reproductive Technology therapy / Diminished Ovarian Reserve (DOR) / Infertilities1
Not AvailableUnknown StatusTreatmentImplantation, Embryo1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous250 ug/0.5mL
Injection, solutionSubcutaneous0.25 mg/0.5mL
SolutionSubcutaneous250 mcg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5767082No1998-06-162015-06-16Us
US6653286No2003-11-252018-06-16Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00531 mg/mLALOGPS
logP3.42ALOGPS
logP1.62ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)9.5ChemAxon
pKa (Strongest Basic)12.14ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count20ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area451.49 Å2ChemAxon
Rotatable Bond Count44ChemAxon
Refractivity423.46 m3·mol-1ChemAxon
Polarizability170.37 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

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 23 more
Substituents
Polypeptide / Alpha peptide / Tyrosine or derivatives / Phenylalanine or derivatives / Leucine or derivatives / N-acyl-alpha amino acid or derivatives / Proline or derivatives / Alpha-amino acid amide / Serine or derivatives / Alanine or derivatives
show 46 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

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. Oberye J, Mannaerts B, Huisman J, Timmer C: Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections. Hum Reprod. 2000 Feb;15(2):245-9. [PubMed:10655292]

Drug created on September 14, 2010 10:21 / Updated on December 12, 2018 07:18