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.
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 1632.29 |
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Degaralix is used for the management of advanced prostate cancer.
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|
GnRH antagonists compete with natural GnRH for binding to GnRH receptors in the pituitary gland. This reversible blinding blocks the release of LH and FSH from the pituitary. The reduction in LH subsequently leads to a rapid and sustained suppression of testosterone release from the testes and subsequently reduces the size and growth of the prostate cancer.
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
90% of the drug is bound to plasma proteins.
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)
Terminal half-life: 41.5 - 70.2 days; Absorption half-life: 32.9 hours; Half-life from injection site: 1.17 days.
Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.
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).
|Pharmacogenomic Effects/ADRs||Not Available|
|Food Interactions||Not Available|
Carin WINDERSTROM, "KIT AND METHOD FOR PREPARATION OF A DEGARELIX SOLUTION." U.S. Patent US20100286603, issued November 11, 2010.US20100286603
|ATC Codes||L02BX02 — Degarelix|
|PDB Entries||Not Available|
|FDA label||Download (448 KB)|
|MSDS||Download (479 KB)|
|Experimental Properties||Not Available|
|Predicted ADMET features|
|Mass Spec (NIST)||Not Available|
|Description||This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.|
|Super Class||Organic Polymers|
|Sub Class||Not Available|
|Alternative Parents||Peptides / Phenylalanine and derivatives / Leucine and derivatives / Proline and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Serine and derivatives / Alanine and derivatives / Amphetamines and derivatives / N-phenylureas / Naphthalenes / Anilides / Pyrrolidinecarboxamides / N-acylpyrrolidines / N-arylamides / Ureides / Pyrimidones / Chlorobenzenes / Aryl chlorides / N-acyl amines / Pyridines and derivatives / Diazinanes / Acetamides / Tertiary carboxylic acid amides / Dicarboximides / Heteroaromatic compounds / Primary carboxylic acid amides / Secondary carboxylic acid amides / Azacyclic compounds / Dialkylamines / Organochlorides / Carbonyl compounds / Organic oxides / Hydrocarbon derivatives / Primary alcohols|
|Substituents||Polypeptide / Alpha peptide / 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 / N-substituted-alpha-amino acid/ Alpha-amino acid or derivatives / N-phenylurea / Naphthalene / Amphetamine or derivatives / Anilide / Pyrrolidine-2-carboxamide / N-arylamide / Pyrrolidine carboxylic acid or derivatives / N-acylpyrrolidine / Chlorobenzene / Ureide / Halobenzene / Pyrimidone / Fatty amide / 1,3-diazinane / Fatty acyl / Aryl chloride / Monocyclic benzene moiety / Aryl halide / N-acyl-amine / Pyrimidine / Pyridine / Benzenoid / Acetamide / Tertiary carboxylic acid amide / Dicarboximide / Heteroaromatic compound / Pyrrolidine / Carboxamide group / Primary carboxylic acid amide / Secondary carboxylic acid amide / Urea / Amino acid or derivatives / Azacycle / Organoheterocyclic compound / Secondary amine / Carboxylic acid derivative / Secondary aliphatic amine / Organooxygen compound / Carbonyl group / Primary alcohol / Organic oxygen compound / Organic nitrogen compound / Alcohol / Hydrocarbon derivative / Organic oxide / Organonitrogen compound / Amine / Organochloride / Organohalogen compound / Aromatic heteropolycyclic compound|
|Molecular Framework||Aromatic heteropolycyclic compounds|
|External Descriptors||Not Available|
- Pharmacological action
- 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 (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 37730.355 Da
- 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. [PubMed:20110043 ]
- 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. [PubMed:20053189 ]
- 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. [PubMed:19450172 ]
- 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. [PubMed:15705170 ]