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GnRH antagonist

Degarelix

Published evidence · coverage incomplete
Anatomical contextAnatomy connections are not mapped yet.

No body region is highlighted until this profile has a supported anatomical connection. This does not mean the peptide has no biological effects.

Read published mechanism findings ↓

At a glance

What is it—and why does it matter?

In a reporter gene assay quantifying competitive antagonism of a GnRH-induced response, degarelix binding affinity was reported as Kd = 0.631 nM. The hazard ratio for BCR-free survival did not show a statistically significant association with assignment to the apalutamide versus placebo arm when both received degarelix. Degarelix (FIRMAGON) is contraindicated for patients with prior severe hypersensitivity to degarelix or any formulation component. Degarelix (FIRMAGON) initiation uses a 240 mg loading regimen administered as two 120 mg subcutaneous injections at 40 mg/mL.

Sources for this introduction: [1] [2] [3] [4]

This published profile is a reference in progress. Findings retain their source context; missing topics are marked below.

What is it?

A molecule, not a product name.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

How does it work?

Target, response, and disposition.

Mechanism

Degarelix acts as a reversible antagonist at pituitary GnRH receptors, decreasing gonadotropin secretion and downstream testosterone production.

Sources[2]dailymedThese highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008Degarelix is a GnRH receptor antagonist. It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone.
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Degarelix is a GnRH receptor antagonist. It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone.”

    These highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008 · 12.1 Mechanism of Action

    dailymed:ab11dd8a-0fd9-4013-89ab-e114557c7e4b:170bb5e2c598:170bb5e2c598

Mechanism

In a cell-based reporter gene assay using HEK293 cells, degarelix showed GnRH receptor antagonist potency quantified by an IC50 of 8.8 nM.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells Assay format: cell-based format Standard result: IC50 = 8.8 nM
Reported result
IC50 = 8.8 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells Assay format: cell-based format Standard result: IC50 = 8.8 nM”

    ChEMBL activities for CHEMBL415606 · Activity 1286227

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Mechanism

Antagonism of GnRH receptors decreases pituitary secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Sources[3]iuphar-commentsIUPHAR ligand commentaryGnRH receptor antagonism reduces the release of the gonadotropins LH and FSH
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “GnRH receptor antagonism reduces the release of the gonadotropins LH and FSH”

    IUPHAR ligand commentary · Mechanism of action

    iuphar-comments:5585:49c5ee6d86f3:49c5ee6d86f3

Mechanism

In a HEK293-cell reporter gene assay, degarelix inhibited GnRH-induced LH secretion (IC50 0.5754 nM).

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Antagonist activity at human GnRH receptor expressed in HEK293 cells as inhibition of GnRH-induced LH secretion by reporter gene assay Assay format: cell-based format Standard result: IC50 = 0.5754 nM
Reported result
IC50 = 0.5754 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Antagonist activity at human GnRH receptor expressed in HEK293 cells as inhibition of GnRH-induced LH secretion by reporter gene assay Assay format: cell-based format Standard result: IC50 = 0.5754 nM”

    ChEMBL activities for CHEMBL415606 · Activity 1721263

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Mechanism

In a reporter gene assay quantifying competitive antagonism of a GnRH-induced response, degarelix binding affinity was reported as Kd = 0.631 nM.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Competitive antagonism of GnRH-induced response in the reporter gene assay Assay format: assay format Standard result: Kd = 0.631 nM
Reported result
Kd = 0.631 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Competitive antagonism of GnRH-induced response in the reporter gene assay Assay format: assay format Standard result: Kd = 0.631 nM”

    ChEMBL activities for CHEMBL415606 · Activity 1286228

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Mechanism

In a HEK293-cell reporter gene assay, degarelix antagonized the human GnRH receptor (IC50 8.8 nM).

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells Assay format: cell-based format Standard result: IC50 = 8.8 nM
Reported result
IC50 = 8.8 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells Assay format: cell-based format Standard result: IC50 = 8.8 nM”

    ChEMBL activities for CHEMBL415606 · Activity 1286227

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Mechanism

In HEK293 cells expressing human GnRH receptor, degarelix antagonized the GnRH response (IC50 1.64 nM).

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Antagonism of GnRH response in HEK293 cells expressing human GnRH receptor Assay format: cell-based format Standard result: IC50 = 1.64 nM
Reported result
IC50 = 1.64 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Antagonism of GnRH response in HEK293 cells expressing human GnRH receptor Assay format: cell-based format Standard result: IC50 = 1.64 nM”

    ChEMBL activities for CHEMBL415606 · Activity 1484981

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

What has been studied?

What the evidence says.

Study findings

Testosterone lowering is stated to be important in the context of testosterone-sensitive prostate cancer.

Sources[3]iuphar-commentsIUPHAR ligand commentaryReducing testosterone levels is important for patients with testosterone-sensitive prostate cancer.
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Reducing testosterone levels is important for patients with testosterone-sensitive prostate cancer.”

    IUPHAR ligand commentary · Mechanism of action

    iuphar-comments:5585:49c5ee6d86f3:49c5ee6d86f3

Study findings

The hazard ratio for BCR-free survival did not show a statistically significant association with assignment to the apalutamide versus placebo arm when both received degarelix.

Sources[4]pubmedFinal Results of the Randomised Phase 2 Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer (ARNEO).BCR-FS was not associated with treatment allocation (hazard ratio 0.72 [95% CI 0.37-1.41]; p = 0.34)
Reported result
hazard ratio 0.72 [95% CI 0.37-1.41]; p = 0.34
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “BCR-FS was not associated with treatment allocation (hazard ratio 0.72 [95% CI 0.37-1.41]; p = 0.34)”

    Final Results of the Randomised Phase 2 Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer (ARNEO). · KEY FINDINGS AND LIMITATIONS

    pubmed:41469270:3a9c5d22ff90:3a9c5d22ff90

Study findings

In a fluorescence assay measuring inhibition of UNG-mediated cleavage/dissociation of quenched duplex DNA oligonucleotides (coupled to APE1), degarelix showed 86.33% inhibition.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Inhibition of UNG by quantifying inhibition of UNG-mediated cleavage and dissociation of quenched duplex DNA oligonucleotides, measured as fluorescence at 594 nm. To generate a functional strand incision and increase turn-over this assay is coupled to APE1. Assay format: assay format Standard result: Inhibition = 86.33 %
Reported result
Inhibition = 86.33 %
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Inhibition of UNG by quantifying inhibition of UNG-mediated cleavage and dissociation of quenched duplex DNA oligonucleotides, measured as fluorescence at 594 nm. To generate a functional strand incision and increase turn-over this assay is coupled to APE1. Assay format: assay format Standard result: Inhibition = 86.33 %”

    ChEMBL activities for CHEMBL415606 · Activity 26252532

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Study findings

In an organism-based Sprague-Dawley rat model, subcutaneous degarelix (50 ug) produced >80.0% inhibition of GnRH-induced LH secretion measured over 120 hrs.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Inhibition of GnRH-induced LH secretion in Sprague-Dawley rat at 50 ug, sc for 120 hrs Assay format: organism-based format Standard result: Inhibition > 80.0 %
Reported result
Inhibition > 80.0 %
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Inhibition of GnRH-induced LH secretion in Sprague-Dawley rat at 50 ug, sc for 120 hrs Assay format: organism-based format Standard result: Inhibition > 80.0 %”

    ChEMBL activities for CHEMBL415606 · Activity 1721365

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Study findings

In a fluorescence-based assay measuring inhibition of OGG1-mediated cleavage/dissociation of quenched duplex DNA oligonucleotides (coupled to APE1), degarelix showed 98.44% inhibition.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Inhibition of OGG1 by quantifying inhibition of OGG1-mediated cleavage and dissociation of quenched duplex DNA oligonucleotides, measured as fluorescence at 594 nm. To generate a functional strand incision and increase turn-over this assay is coupled to APE1. Assay format: assay format Standard result: Inhibition = 98.44 %
Reported result
Inhibition = 98.44 %
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Inhibition of OGG1 by quantifying inhibition of OGG1-mediated cleavage and dissociation of quenched duplex DNA oligonucleotides, measured as fluorescence at 594 nm. To generate a functional strand incision and increase turn-over this assay is coupled to APE1. Assay format: assay format Standard result: Inhibition = 98.44 %”

    ChEMBL activities for CHEMBL415606 · Activity 26249547

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Study findings

In a SARS-CoV-2 cytopathic effect assay in VERO-E6 cells (0.01 MOI; 48 hours; high-content imaging), degarelix potency was IC50 = 20650.0 nM.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of VERO-E6 cells after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Assay format: organism-based format Standard result: IC50 = 20650.0 nM
Reported result
IC50 = 20650.0 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of VERO-E6 cells after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Assay format: organism-based format Standard result: IC50 = 20650.0 nM”

    ChEMBL activities for CHEMBL415606 · Activity 20154236

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Study findings

In a SARS-CoV-2 cytopathic effect assay in Caco-2 cells (high-content imaging), degarelix produced 2.6% inhibition at 10 uM after 48 hours.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL415606Assay: Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Assay format: organism-based format Standard result: Inhibition = 2.6 %
Reported result
Inhibition = 2.6 %
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Assay format: organism-based format Standard result: Inhibition = 2.6 %”

    ChEMBL activities for CHEMBL415606 · Activity 18834076

    chembl-activities:chembl415606:73c3afbd1817:73c3afbd1817

Risks and interactions

Risks, organized for scanning.

Contraindications

Degarelix (FIRMAGON) is contraindicated for patients with prior severe hypersensitivity to degarelix or any formulation component.

Sources[2]dailymedThese highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008FIRMAGON is contraindicated in patients with history of severe hypersensitivity to degarelix or to any of the product components[seeWarnings and Precautions (5.1)].
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “FIRMAGON is contraindicated in patients with history of severe hypersensitivity to degarelix or to any of the product components[seeWarnings and Precautions (5.1)].”

    These highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008 · 4 CONTRAINDICATIONS

    dailymed:ab11dd8a-0fd9-4013-89ab-e114557c7e4b:170bb5e2c598:170bb5e2c598

Products and regulatory status

Same ingredient. Different records.

Regulatory status

Degarelix (FIRMAGON) has an approved indication for treating patients with advanced prostate cancer.

Sources[2]dailymedThese highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008FIRMAGON®is indicated for treatment of patients with advanced prostate cancer.[3]iuphar-commentsIUPHAR ligand commentaryApproved to treat patients with advanced prostate cancer.
Source records
2
Independent studies
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “FIRMAGON®is indicated for treatment of patients with advanced prostate cancer.”

    These highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008 · 1 INDICATIONS AND USAGE

    dailymed:ab11dd8a-0fd9-4013-89ab-e114557c7e4b:170bb5e2c598:170bb5e2c598
  2. supports · Source-backed record
    “Approved to treat patients with advanced prostate cancer.”

    IUPHAR ligand commentary · Clinical use

    iuphar-comments:5585:49c5ee6d86f3:49c5ee6d86f3

Administration context

The practical clinical context.

Dose records

Degarelix (FIRMAGON) initiation uses a 240 mg loading regimen administered as two 120 mg subcutaneous injections at 40 mg/mL.

Sources[2]dailymedThese highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL”

    These highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008 · 2.1 Dosing information

    dailymed:ab11dd8a-0fd9-4013-89ab-e114557c7e4b:170bb5e2c598:170bb5e2c598

Research status + gaps

What still needs better answers?

  • No publishable claim yet for: administration, identity, interaction, safety
  • 110 compiled claim(s) withheld by automated assurance: assurance_score_below_0.58 (50), assurance_score_below_0.72 (57), current_regulatory_source_required (22), extraction_ambiguity (66), high_risk_requires_regulatory_or_two_independent_sources (58), no_direct_support (103)

These are the limits of this profile, not an exhaustive list of scientific uncertainties.

References + discovery

Open the records yourself.

  1. ChEMBL activities for CHEMBL415606 ↗

    chembl-activities · published 2026-08-26 · retrieved 2026-08-26T08:42:26Z

  2. These highlights do not include all the information needed to use FIRMAGON safely and effectively. See full prescribing information for FIRMAGON.FIRMAGON®(degarelix for injection) for subcutaneous useInitial U.S. Approval: 2008 ↗

    dailymed · published 2024-01-30 · retrieved 2026-09-04T19:33:10Z

  3. IUPHAR ligand commentary ↗

    iuphar-comments · published 2026-08-26 · retrieved 2026-08-26T08:42:26Z

  4. Final Results of the Randomised Phase 2 Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer (ARNEO). ↗

    pubmed · published 2026-06-01 · retrieved 2026-08-26T08:42:26Z

Publication history and provenance

Version 7 · Automated assessment · 2026-09-04T19:33:10Z

0deeee073cc83ae8d301d1d1501369cc2720362a3bd340c07dd152d8d284b4c1