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Five of its ten residues are unnatural, and four are D-amino acids: ganirelix is GnRH rebuilt so thoroughly that it blocks the receptor it was copied from.
Also known as: Orgalutran · Antagon · Fyremadel · ganirelix acetate · RS-26306 · Org 37462
Part of the Foundational & therapeutic peptides cluster
Overview
Ganirelix is a synthetic third-generation GnRH antagonist decapeptide, approved by the FDA and EMA to prevent premature luteinising-hormone surges in women undergoing controlled ovarian stimulation for IVF. Five of its ten residues are unnatural amino acids that let it bind the pituitary GnRH receptor competitively without activating it, so suppression is immediate and reversible. After subcutaneous injection it peaks in 1–2 hours with over 90% bioavailability; in a large multicentre trial the 0.25 mg daily dose gave a vital pregnancy rate of 40.3% per embryo transfer.
Source & context
Biological / chemical source: Synthetic decapeptide analog of GnRH
Primary research or clinical context: Approved prescription medicine (FDA, EMA) to prevent premature LH surges during controlled ovarian stimulation in assisted reproduction
What ganirelix is
Ganirelix is a synthetic decapeptide antagonist of gonadotropin-releasing hormone, developed by Organon (originally coded RS-26306 at Syntex) and approved in 1999 for one specific job: preventing the premature luteinising-hormone surge that would otherwise trigger ovulation before egg retrieval during controlled ovarian stimulation for IVF. It competitively blocks the GnRH receptor on pituitary gonadotrophs, so LH and FSH release from endogenous GnRH stops within hours of the first injection and resumes within days of the last (Gillies et al., Drugs 2000; Mannaerts, F&S Reports 2023). Formula C80H113ClN18O13, average mass about 1,570 Da — heavy for a decapeptide because of its bulky unnatural side chains.
Sequence and engineering
The selected reference backbone XXXSYXLXPA uses X for the noncanonical residues at positions 1, 2, 3, 6 and 8. Positions 1 to 3 are N-acetyl-D-2-naphthylalanine, D-4-chlorophenylalanine and D-3-pyridylalanine, a hydrophobic D-amino-acid cluster that binds the receptor without activating it. Positions 6 and 8 carry N9,N10-diethyl-homoarginine, with D configuration at 6 and L configuration at 8; position 10 is D-alaninamide. Haviv et al. (Pharmaceutical Biotechnology 1998) describe the design logic of this generation: unnatural side chains and D-amino acids, with the combination of a hydrophobic N-terminus and a basic C-terminus at 6 and 8 having caused histamine-release reactions in earlier antagonists — a problem greatly reduced by the specific substitutions at positions 5, 6 and 8 that ganirelix uses.
Mechanism: antagonist, not agonist
The GnRH agonists used in the older “long protocol” — buserelin, leuprolide, triptorelin — suppress the pituitary only after an initial flare and a week or more of desensitisation. Ganirelix binds the same receptor competitively and has no intrinsic activity, so suppression begins with the first dose and there is no flare. Because binding is reversible, the pituitary recovers within days of stopping, which allows the final oocyte-maturation trigger to be given with a GnRH agonist rather than hCG in patients at risk of ovarian hyperstimulation syndrome (Mannaerts 2023).
Pharmacokinetics and dosing in trials
After subcutaneous injection ganirelix is absorbed rapidly, reaching peak plasma levels within 1 to 2 hours, with absolute bioavailability above 90% (Mannaerts 2023). The 0.25 mg daily dose used in every approved regimen was selected in a phase II dose-finding study as the minimal effective daily dose to prevent premature LH surges and the one that yielded the highest ongoing pregnancy rate per started cycle. It is given daily from the mid-follicular phase of stimulation until the trigger day. This section describes the trial-derived regimen; it is not prescribing guidance.
Clinical evidence
In a large multicentre trial in women undergoing IVF, ganirelix effectively inhibited LH surges during controlled ovarian stimulation, and the 0.25 mg/day dose achieved a vital pregnancy rate per embryo transfer of 40.3% at weeks 5 to 6 (Gillies et al., Drugs 2000). Three large phase III trials compared ganirelix with the agonists buserelin, leuprolide and triptorelin in a long protocol (Out and Mannaerts, Human Fertility 2002). Combined analyses found antagonist protocols need less FSH, shorten stimulation, reduce ovarian hyperstimulation syndrome and reduce patient burden, with a trend toward a slightly lower ongoing pregnancy rate that is largely eliminated when a GnRH-agonist trigger is used (Mannaerts 2023). A 2023 systematic review and network meta-analysis of 102 publications compared antagonist protocols — fixed versus flexible start, ganirelix versus cetrorelix, with or without pretreatment — on live birth and ongoing pregnancy (Venetis et al., Human Reproduction Update 2023).
| Outcome | Antagonist (ganirelix) | Long agonist |
|---|---|---|
| Onset of suppression | Immediate, no flare | After initial flare and ~2 weeks |
| FSH requirement | Lower | Higher |
| Duration of stimulation | Shorter | Longer |
| Ovarian hyperstimulation syndrome | Reduced | Higher |
| Ongoing pregnancy rate | Trend slightly lower; gap closed with agonist trigger | Reference |
Side effects
Ganirelix has been generally well tolerated. The most common adverse events in trials were local injection-site reactions, asthenia, nausea, malaise, headache and fatigue (Gillies et al. 2000). Histamine-release reactions, the problem of earlier antagonist generations, were designed out. As with any GnRH antagonist, use in pregnancy is contraindicated. Prescribing information covers monitoring; this profile does not.
Ganirelix vs cetrorelix, and a note on generics
Cetrorelix is the other approved GnRH antagonist for IVF, given either daily at 0.25 mg or as a single 3 mg depot. The 2023 network meta-analysis found the two broadly comparable, with protocol timing mattering more than the choice of molecule (Venetis et al. 2023). Ganirelix generics (marketed as Fyremadel and others) exist; because the peptide carries six unnatural residues, its manufacturing impurity profile is complex — a 2023 paper synthesised and characterised two des-ethyl-ganirelix impurities specifically so generic formulations could be compared with the reference product (Chatterjee and Bandyopadhyay, Journal of Peptide Science 2023). As of September 2026, 105 registered trials list ganirelix as an intervention.
Sequence of the selected reference form
Sequence backbone for the reference form: Ganirelix anhydrous parent free base. Termini, stereochemistry and modifications are described below.
XXXSYXLXPA
X1=Ac-D-2Nal; X2=D-4-chlorophenylalanine; X3=D-3-pyridylalanine; X6=D-N9,N10-diethyl-homoarginine; X8=L-N9,N10-diethyl-homoarginine; A10=D-alaninamide.. X marks a noncanonical residue; see the expanded sequence and reference chemistry below.
Analyze sequences in the playground →Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
The selected fully defined decapeptide agrees with the official label and NIH GSRS. N9,N10-diethyl-homoarginines6/8 and the specified D/L configurations must be retained. The old CID contains undefined and conflicting stereochemistry; the selected label mass excludes acetate.
- Molecular form
- Ganirelix anhydrous parent free base
- Species
- Synthetic GnRH antagonist; no natural source species applies
- Termini (N / C)
- N-acetyl-D-2-naphthylalanyl / D-alaninamide
Average reference mass · Molecular identity assessment: 2026-10-05
Reference policy updated: 2026-10-05
- PubChem PUG REST selected parent properties · 2026-10-05
- PubChem selected-parent biologic notation · 2026-10-05
- PubChem selected-parent identifiers with depositor attribution · 2026-10-05
- NIH GSRS independently selected parent record · 2026-10-05
Ac-D-2Nal-D-Phe(4-Cl)-D-3Pal-Ser-Tyr-D-hArg(Et,Et)-Leu-hArg(Et,Et)-Pro-D-Ala-NH2
- Molecular formula
- C80H113ClN18O13
- Average reference mass
- ≈ 1,570.4
- Plasma half-life
- Rapidly absorbed after subcutaneous injection (tmax 1–2 h); absolute bioavailability over 90%; suppression is immediately reversible on stopping
- Receptors
- Competitive antagonist at the pituitary GnRH receptor; no intrinsic activity, so no initial flare
- Backbone
- Ganirelix anhydrous parent free base
- C-terminus
- D-alaninamide
- Status
- Approved (FDA 1999, EMA): prevention of premature LH surges in controlled ovarian stimulation; generics available
- PubChem CID: 16130957
- CAS RN: 124904-93-4
- UNII: IX503L9WN0
Chemistry values: curated profile, PubChem.
Clinical development snapshot
ClinicalTrials.gov lists 105 registered studies with “Ganirelix” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07732348 | Oral GnRH Antagonist (Linzagolix) Versus Injectable GnRH Antagonist in Controlled Ovarian Stimulation for In V | Not applicable | not yet recruiting | 2026-09-30 |
| NCT07108621 | hCG Priming in Women With Diminished Ovarian Reserve | Phase 3 | recruiting | 2026-09-21 |
| NCT06280560 | Impact of IVF Hormonal Therapy on Endometrial Receptivity and Endometrial Senescent Cell Pathological Accumula | — | recruiting | 2026-09-04 |
| NCT06745466 | Disentangling the Effects of Daily Stress, Sleep, and Sex Hormones on Accelerated Vascular Aging in Midlife Wo | Phase 4 | recruiting | 2026-07-02 |
| NCT06877429 | Is the Diurnal Variation in Circulating Levels of Cortisol Reflected in Follicular Fluid of Preovulatory Folli | — | not yet recruiting | 2026-05-07 |
| NCT04983173 | INTEnsity of ovariaN Stimulation and Embryo Quality | Phase 4 | completed | 2026-04-14 |
Ganirelix — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Ganirelix anhydrous parent free baseAverage reference mass: 1,570.4 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Ganirelix
What is Ganirelix?+
Ganirelix is a synthetic third-generation GnRH antagonist decapeptide, approved by the FDA and EMA to prevent premature luteinising-hormone surges in women undergoing controlled ovarian stimulation for IVF. Five of its ten residues are unnatural amino acids that let it bind the pituitary GnRH receptor competitively without activating it, so suppression is immediate and reversible. After subcutaneous injection it peaks in 1–2 hours with over 90% bioavailability; in a large multicentre trial the 0.25 mg daily dose gave a vital pregnancy rate of 40.3% per embryo transfer.
What Canadian product status is recorded for Ganirelix?+
Canadian product status for Ganirelix has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the length of the selected reference form for Ganirelix?+
The selected reference form (Ganirelix anhydrous parent free base) has 10 residues or residue-derived units in its backbone. Other forms in this family may have a different length.
What is ganirelix?+
A synthetic decapeptide GnRH antagonist, approved to prevent premature LH surges during ovarian stimulation for IVF. Sold as Orgalutran, Antagon and generics such as Fyremadel.
How does ganirelix work?+
It competitively blocks the pituitary GnRH receptor without activating it, so LH and FSH release stops immediately, with no flare, and recovers within days of stopping.
What is the difference between ganirelix and a GnRH agonist like leuprolide?+
Agonists suppress the pituitary only after a flare and about two weeks of desensitisation; ganirelix suppresses at once and reversibly, needs less FSH, shortens stimulation and lowers hyperstimulation risk.
Ganirelix vs cetrorelix — which is better?+
A 2023 network meta-analysis found them broadly comparable; protocol timing (fixed vs flexible start) matters more than the molecule.
What are the side effects of ganirelix?+
Injection-site reactions, asthenia, nausea, malaise, headache and fatigue were the most common in trials; it is generally well tolerated.
What is the sequence of ganirelix?+
Ac-D-Nal-D-Cpa-D-Pal-Ser-Tyr-D-hArg(Et2)-Leu-hArg(Et2)-Pro-D-Ala-NH2 — five unnatural residues on a GnRH backbone; formula C80H113ClN18O13, mass about 1,570 Da.
Further reading
- PK conceptsWhy Peptides Have Short Half-Lives (And How Engineers Fix It)Proteases, renal clearance, DPP-4, PEGylation, lipidation, cyclization—educational guide to peptide pharmacokinetics concepts.
- FoundationsWhat Are Research Peptides? A Clear Educational GuideLearn what “research peptides” means, how they differ from approved peptide drugs, quality markers (COA, purity), and how to study them responsibly.
Related peptides
References & further reading
- 1.Gillies et al. (2000). Ganirelix. Drugs
- 2.Oberyé et al. (1999). Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part II. Dose-proportionality and gonadotropin suppression after multiple doses of ganirelix in healthy female volunteers. Fertil Steril
- 3.Oberyé et al. (1999). Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers. Fertil Steril
- 4.Han et al. (2022). Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study. J Obstet Gynaecol
- 5.de Jong et al. (2001). Dynamics of the development of multiple follicles during ovarian stimulation for in vitro fertilization using recombinant follicle-stimulating hormone (Puregon) and various doses of the gonadotropin-releasing hormone antagonist ganirelix (Orgalutran/Antagon). Fertil Steril
- 6.Russo et al. (2011). Effects of the gonadotropin-releasing hormone antagonist ganirelix on normal micturition and prostaglandin E(2)-induced detrusor overactivity in conscious female rats. Eur Urol
- 7.Beguería et al. (2019). Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod
- 8.Borm et al. (2000). Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial. The European Orgalutran Study Group. Hum Reprod
- 9.Mannaerts (2023). Ganirelix and the prevention of premature luteinizing hormone surges. F&S Reports
- 10.Out & Mannaerts (2002). The gonadotrophin-releasing hormone antagonist ganirelix — history and introductory data. Human Fertility
- 11.Venetis et al. (2023). What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis. Human Reproduction Update
- 12.Haviv et al. (1998). LHRH antagonists. Pharmaceutical Biotechnology
- 13.Chatterjee & Bandyopadhyay (2023). Synthesis and characterization of two potential impurities (des-ethyl-Ganirelix) generated in the Ganirelix manufacturing process. Journal of Peptide Science
- 14.IUPHAR/BPS Guide to Pharmacology — ganirelix (ligand 3877)
- 15.PubChem — Ganirelix (CID 16130966)