Degarelix

Degarelix is a synthetic decapeptide (10 amino acids) and a third-generation gonadotropin-releasing hormone (GnRH) receptor antagonist. It is approved for the treatment of advanced hormone-dependent prostate cancer. Unlike GnRH agonists, degarelix directly blocks GnRH receptors in the pituitary gland without causing an initial testosterone surge (clinical flare), providing immediate and sustained testosterone suppression to castration levels. Its unique molecular structure incorporates non-natural amino acids including D-2-naphthylalanine, D-4-chlorophenylalanine, and D-3-pyridylalanine, which confer high binding affinity (IC50 = 3 nM) and selectivity for the GnRH receptor with minimal histamine release.