A synthetic GNRHR antagonist
Degarelix is a synthetic gonadotropin-releasing hormone receptor (GNRHR) antagonist (IC50 = 3 nM in HEK293 cells expressing the human receptor).1 It inhibits the growth of WPMY-1, WPE1-NA22, BPH-1, and LNCaP prostate cell lines following a 72-hour incubation at a concentration of 10 μM via caspase activation and induction of apoptosis.2 In vivo, degarelix (2 mg/kg) decreases plasma testosterone levels in rats to castrate levels for the first 49 days post administration.1 It decreases tumor volume of Dunning R3327H prostate tumor flank implants in rats when administered at a dose of 1 mg/kg per month.3 Formulations containing degarelix have been used in the treatment of advanced prostate cancer.
1.Jiang, G., Stalewski, J., Galyean, R., et al.GnRH antagonists: A new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6J. Med. Chem.44(3)453-467(2001) 2.Sakai, M., Martinez-Arguelles, D.B., Patterson, N.H., et al.In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonist degarelix on human prostate cell growthPLoS One10(3)e0120670(2015) 3.Princivalle, M., Broqua, P., White, R., et al.Rapid suppression of plasma testosterone levels and tumor growth in the dunning rat model treated with degarelix, a new gonadotropin-releasing hormone antagonistJ. Pharmacol. Exp. Ther.320(3)1113-1118(2007)
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