DT-Web

DB06699 - Degarelix


Identification
Name Degarelix
Accession Number DB06699
Type small molecule
Description 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1632.259
Groups approved
Monoisotopic Weight 1630.748797045
Pharmacology
Indication Degaralix is used for the management of advanced prostate cancer.
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.
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.
Protein binding 90% of the drug is bound to plasma proteins.
Biotransformation 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)
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).
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mifepristone Enhance QTc-prolonging effect
Food Interactions Not Available

Targets


Gonadotropin-releasing hormone receptor
Name Gonadotropin-releasing hormone receptor
Gene Name GNRHR
Pharmacological action yes
Actions antagonist
References
  • Steinberg M: Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther. 2009;31 Pt 2:2312-31. - Pubmed
  • Kirby RS, Fitzpatrick JM, Clarke N: Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. BJU Int. 2009 Dec;104(11):1580-4. - Pubmed
  • Anderson J: Degarelix: a novel gonadotropin-releasing hormone blocker for the treatment of prostate cancer. Future Oncol. 2009 May;5(4):433-43. - Pubmed
  • 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
DTHybrid score 1.3256

Predictions


Id Partner name Gene Name Score
148 Lutropin-choriogonadotropic hormone receptor LHCGR 0.2629
3811 Cytochrome P450 19A1 CYP19A1 0.0487
1649 Small inducible cytokine A2 CCL2 0.0242
756 Sex hormone-binding globulin SHBG 0.017
614 Progesterone receptor PGR 0.0157
146 Androgen receptor AR 0.0135
136 Estrogen receptor ESR1 0.0125
4512 Cytochrome P450 3A4 CYP3A4 0.0079
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