tcsc5350 Degarelix

Degarelix is a competitive and reversible gonadotropin-releasing hormone receptor (GnRHR) antagonist.

IC50 & Target: GnRHR^[1]

In Vitro: Degarelix acts directly on the pituitary receptors for luteinizing hormone-releasing hormone (LHRH), blocking the action of endogenous LHRH. The use of degarelix eliminates the initial undesirable surge in gonadotropin and testosterone levels, which is produced by agonists of LHRH^[1]. Degarelix treatment reduces cell viability in all prostate cell lines (WPE1-NA22, WPMY-1, BPH-1 cells, VCaP cells), with the exception of the PC-3 cells. The GnRH antagonist degarelix exerts a direct effect on prostate cell growth through apoptosis^[2].

In Vivo: At single subcutaneous injections of 0.3 to 10 μg/kg in rats, degarelix produces a dose-dependent suppression of the pituitary-gonadal axis as revealed by the decrease in plasma luteinizing hormone (LH) and testosterone levels. Duration of LH suppression increases with the dose: in the rat, significant suppression of LH lasted 1, 2, and 7 days after a single subcutaneous injection of degarelix at 12.5, 50, or 200 μg/kg, respectively^[3]. Degarelix is stable when incubated in microsomes and cryopreserved hepatocytes from animal liver tissue. In rat and dog, most of the degarelix dose is eliminated within 48 h via urine and feces in equal amounts (40–50% in each matrix), whereas in monkey the major route of excretion is fecal (50%) and renal (22%)^[4].