Degarelix
Identification
- Summary
Degarelix is a GnRH receptor antagonist used in the management of advanced prostate cancer.
- Brand Names
- Firmagon
- Generic Name
- Degarelix
- DrugBank Accession Number
- DB06699
- Background
Degarelix is used for the treatment of advanced prostate cancer. Degarelix is a synthetic peptide derivative drug which binds to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and blocks interaction with GnRH. This antagonism reduces luteinising hormone (LH) and follicle-stimulating hormone (FSH) which ultimately causes testosterone suppression. Reduction in testosterone is important in treating men with advanced prostate cancer. Chemically, it is a synthetic linear decapeptide amide with seven unnatural amino acids, five of which are D-amino acids. FDA approved on December 24, 2008.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Degarelix (DB06699)
- Weight
- Average: 1632.29
Monoisotopic: 1630.748797 - Chemical Formula
- C82H103ClN18O16
- Synonyms
- Degarelix
- External IDs
- FE200486
Pharmacology
- Indication
Degaralix is used for the management of advanced prostate cancer.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Degarelix is a synthetic derivative of GnRH decapeptide, the ligand of the GnRH receptor. Gonadotropin and androgen production result from the binding of endogenous GnRH to the GnRH receptor. Degarelix antagonizes the GnRH receptor which in turn blocks the release of LH and FSH from the pituitary. LF and FSH decreases in a concentration-dependent manner. The reduction in LH leads to a decrease in testosterone release from the testes.
- Mechanism of action
Degarelix competitively inhibits GnRH receptors in the pituitary gland, preventing the release of luteinizing hormone (LH) and follicle stimulating hormone. Reduced LH suppresses testosterone release, which slows the growth and reduces the size of prostate cancers.
Target Actions Organism AGonadotropin-releasing hormone receptor antagonistHumans - Absorption
Degarelix forms a depot at the site of injection after subcutaneous administration from which the drug slowly released into circulation. After a single bolus dose of 2mg/kg, peak plasma concentrations of degarelix occured within 6 hours at a concentration of 330 ng/mL. Ki = 0.082 ng/mL and 93% of receptors were fully suppressed; MRT = 4.5 days.
- Volume of distribution
Central compartment: 8.88 - 11.4 L; Peripheral compartment: 40.9 L
- Protein binding
90% of the drug is bound to plasma proteins.
- Metabolism
70% - 80% of degarelix is subject to peptide hydrolysis during its passage through the hepatobiliary system and then fecally eliminated. No active or inactive metabolites or involvement of CYP450 isozymes.
- Route of elimination
Fecal (70% to 80%) and renal (20%-30% of unchanged drug)
- Half-life
Terminal half-life: 41.5 - 70.2 days; Absorption half-life: 32.9 hours; Half-life from injection site: 1.17 days.
- Clearance
Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most commonly observed adverse reactions (> 10%) during degarelix therapy included injection site reactions (e.g., pain, erythema, swelling, or induration), hot flashes, increased weight, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcrivastine The risk or severity of QTc prolongation can be increased when Degarelix is combined with Acrivastine. Adenosine The risk or severity of QTc prolongation can be increased when Degarelix is combined with Adenosine. Ajmaline The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Degarelix. Alfuzosin The risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Degarelix. Alimemazine The risk or severity of QTc prolongation can be increased when Alimemazine is combined with Degarelix. Amantadine The risk or severity of QTc prolongation can be increased when Amantadine is combined with Degarelix. Amifampridine The risk or severity of QTc prolongation can be increased when Degarelix is combined with Amifampridine. Amiodarone The risk or severity of QTc prolongation can be increased when Degarelix is combined with Amiodarone. Amisulpride The risk or severity of QTc prolongation can be increased when Amisulpride is combined with Degarelix. Amitriptyline The risk or severity of QTc prolongation can be increased when Degarelix is combined with Amitriptyline. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Degarelix acetate hydrate EXT215F4ZU 934246-14-7 AUTFSFUMNFDPLH-KYMMNHPFSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Firmagon Powder, metered 40 mg/1mL Subcutaneous Ferring Pharmaceuticals 2009-03-02 2015-03-31 US 
Firmagon Powder, for solution 120 mg / vial Subcutaneous Ferring Pharmaceuticals 2009-11-24 Not applicable Canada 
Firmagon Powder, metered 40 mg/1mL Subcutaneous Ferring Pharmaceuticals Inc. 2009-03-02 Not applicable US Firmagon Injection, powder, for solution 120 mg Subcutaneous Ferring Pharmaceuticals 2016-09-08 Not applicable EU 
Firmagon Powder, for solution 80 mg / vial Subcutaneous Ferring Pharmaceuticals 2009-11-24 Not applicable Canada Firmagon Powder, metered 20 mg/1mL Subcutaneous Ferring Pharmaceuticals 2009-03-02 2015-03-31 US Firmagon Injection, powder, for solution 80 mg Subcutaneous Ferring Pharmaceuticals 2016-09-08 Not applicable EU Firmagon Powder, metered 20 mg/1mL Subcutaneous Ferring Pharmaceuticals Inc. 2009-03-02 Not applicable US Firmagon Injection, powder, for solution 80 mg Subcutaneous Ferring Pharmaceuticals 2016-09-08 Not applicable EU
Categories
- ATC Codes
- L02BX02 — Degarelix
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Decreased GnRH Secretion
- Endocrine Therapy
- Gonadotropin Releasing Hormone Receptor Antagonists
- Gonadotropin-releasing Hormone Antagonists
- Gonadotropin-Releasing Hormone, antagonists & inhibitors
- Hormone Antagonists and Related Agents
- Peptides
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- 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 / 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 / N-phenylureas / Naphthalenes show 26 more
- Substituents
- 1,3-diazinane / Acetamide / Alanine or derivatives / Alcohol / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Amphetamine or derivatives show 54 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- SX0XJI3A11
- CAS number
- 214766-78-6
- InChI Key
- MEUCPCLKGZSHTA-XYAYPHGZSA-N
- InChI
- InChI=1S/C82H103ClN18O16/c1-45(2)35-60(72(107)92-59(16-9-10-33-87-46(3)4)80(115)101-34-12-17-68(101)79(114)88-47(5)70(84)105)93-74(109)63(38-51-23-30-58(31-24-51)91-81(85)116)95-76(111)64(39-50-21-28-57(29-22-50)90-71(106)66-42-69(104)100-82(117)99-66)97-78(113)67(44-102)98-77(112)65(41-53-13-11-32-86-43-53)96-75(110)62(37-49-19-26-56(83)27-20-49)94-73(108)61(89-48(6)103)40-52-18-25-54-14-7-8-15-55(54)36-52/h7-8,11,13-15,18-32,36,43,45-47,59-68,87,102H,9-10,12,16-17,33-35,37-42,44H2,1-6H3,(H2,84,105)(H,88,114)(H,89,103)(H,90,106)(H,92,107)(H,93,109)(H,94,108)(H,95,111)(H,96,110)(H,97,113)(H,98,112)(H3,85,91,116)(H2,99,100,104,117)/t47-,59+,60+,61-,62-,63-,64+,65-,66+,67+,68+/m1/s1
- IUPAC Name
- (4S)-N-{4-[(2S)-2-{[(1R)-2-[4-(carbamoylamino)phenyl]-1-{[(1S)-1-{[(2S)-1-[(2S)-2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl]-1-oxo-6-[(propan-2-yl)amino]hexan-2-yl]carbamoyl}-3-methylbutyl]carbamoyl}ethyl]carbamoyl}-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]ethyl]phenyl}-2,6-dioxo-1,3-diazinane-4-carboxamide
- SMILES
- CC(C)C[C@H](NC(=O)[C@@H](CC1=CC=C(NC(N)=O)C=C1)NC(=O)[C@H](CC1=CC=C(NC(=O)[C@@H]2CC(=O)NC(=O)N2)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=CC=C2C=CC=CC2=C1)NC(C)=O)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O
References
- Synthesis Reference
Carin WINDERSTROM, "KIT AND METHOD FOR PREPARATION OF A DEGARELIX SOLUTION." U.S. Patent US20100286603, issued November 11, 2010.
US20100286603- General References
- Steinberg M: Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther. 2009;31 Pt 2:2312-31. doi: 10.1016/j.clinthera.2009.11.009. [Article]
- Persson BE, Kold Olesen T, Jensen JK: Degarelix: a new approach for the treatment of prostate cancer. Neuroendocrinology. 2009;90(3):235-44. doi: 10.1159/000228832. Epub 2009 Jul 14. [Article]
- External Links
- KEGG Drug
- D08901
- PubChem Compound
- 16136245
- PubChem Substance
- 99443253
- ChemSpider
- 17292756
- BindingDB
- 50102450
- 475230
- ChEBI
- 135961
- ChEMBL
- CHEMBL415606
- PharmGKB
- PA165958373
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Degarelix
- FDA label
- Download (448 KB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Prostate Cancer 1 4 Completed Other Cardiovascular Disease (CVD) / Prostatic Neoplasms 1 4 Not Yet Recruiting Basic Science Aging / Hypoestrogenism / Menopause / Women 1 4 Recruiting Basic Science Aging / Menopause / Obesity, Abdominal / Weight Gain 1 4 Recruiting Supportive Care Prostatic Neoplasms 1 4 Terminated Treatment Prostate Cancer - Recurrent 1 4 Unknown Status Other Prostate Cancer 1 3 Active Not Recruiting Treatment Prostate Cancer 1 3 Completed Treatment Endometriosis 1 3 Completed Treatment Infertility / OHSS / Polycystic Ovarian Syndrome (PCOS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Parenteral; Subcutaneous 120 MG Injection, powder, for solution Parenteral; Subcutaneous 80 MG Powder, for solution Subcutaneous 120 mg / vial Powder, for solution Subcutaneous 80 mg / vial Powder, metered Subcutaneous 20 mg/1mL Powder, metered Subcutaneous 40 mg/1mL Injection, powder, lyophilized, for solution Subcutaneous 120 mg Injection, powder, lyophilized, for solution Subcutaneous 80 mg Powder Subcutaneous Injection, powder, for solution Subcutaneous 120 mg Injection, powder, for solution Subcutaneous 80 mg Powder Subcutaneous 120 mg/1vial Powder Subcutaneous 80 mg/1vial - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2286190 No 2007-01-09 2018-04-13 Canada US5925730 No 1999-07-20 2021-05-18 US US9579359 No 2017-02-28 2029-02-10 US US9415085 No 2016-08-16 2032-04-27 US US10695398 No 2020-06-30 2032-04-27 US US10729739 No 2020-08-04 2029-02-10 US US10973870 No 2009-02-10 2029-02-10 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0041 mg/mL ALOGPS logP 2.66 ALOGPS logP 0.18 ChemAxon logS -5.6 ALOGPS pKa (Strongest Acidic) 10.55 ChemAxon pKa (Strongest Basic) 11.16 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 18 ChemAxon Hydrogen Donor Count 17 ChemAxon Polar Surface Area 512.87 Å2 ChemAxon Rotatable Bond Count 41 ChemAxon Refractivity 431.13 m3·mol-1 ChemAxon Polarizability 168.98 Å3 ChemAxon Number of Rings 8 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8352 Blood Brain Barrier - 0.953 Caco-2 permeable - 0.7556 P-glycoprotein substrate Substrate 0.8461 P-glycoprotein inhibitor I Non-inhibitor 0.6672 P-glycoprotein inhibitor II Non-inhibitor 0.7791 Renal organic cation transporter Non-inhibitor 0.8579 CYP450 2C9 substrate Non-substrate 0.7299 CYP450 2D6 substrate Non-substrate 0.8156 CYP450 3A4 substrate Substrate 0.6482 CYP450 1A2 substrate Non-inhibitor 0.8566 CYP450 2C9 inhibitor Non-inhibitor 0.6493 CYP450 2D6 inhibitor Non-inhibitor 0.8566 CYP450 2C19 inhibitor Non-inhibitor 0.7291 CYP450 3A4 inhibitor Non-inhibitor 0.5961 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8478 Ames test Non AMES toxic 0.652 Carcinogenicity Non-carcinogens 0.7848 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.7005 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8534 hERG inhibition (predictor II) Inhibitor 0.5235
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
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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
- Steinberg M: Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther. 2009;31 Pt 2:2312-31. doi: 10.1016/j.clinthera.2009.11.009. [Article]
- Kirby RS, Fitzpatrick JM, Clarke N: Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. BJU Int. 2009 Dec;104(11):1580-4. doi: 10.1111/j.1464-410X.2009.08924.x. [Article]
- Anderson J: Degarelix: a novel gonadotropin-releasing hormone blocker for the treatment of prostate cancer. Future Oncol. 2009 May;5(4):433-43. doi: 10.2217/fon.09.24. [Article]
- Samant MP, Miller C, Hong DJ, Koerber SC, Croston G, Rivier CL, Rivier JE: Synthesis and biological activity of GnRH antagonists modified at position 3 with 3-(2-methoxy-5-pyridyl)-alanine. J Pept Res. 2005 Feb;65(2):284-91. [Article]
Drug created on May 06, 2010 16:15 / Updated on October 16, 2021 12:31