FE200486

Degarelix acetate hydrate is a competitive and reversible gonadotropin-releasing hormone receptor (GnRHR/LHRHR) antagonist. Degarelix acetate hydrate can be used for prostate cancer research[1].

Signaling Pathways >> GPCR/G Protein >> GNRH Receptor

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Endocrinology

Degarelix shows only very weak histamine-releasing properties and the lowest capacity for histamine release among the antagonists of LHRH, including Cetrorelix (HY-P0009), Abarelix (HY-13534), and Ganirelix (HY-P1628)[1]. Degarelix (1 nM-10 μM, 0-72 h) reduces cell viability in all prostate cell lines (WPE1-NA22, WPMY-1, BPH-1, VCaP cells), with the exception of the PC-3 cells[2]. Degarelix (10 μM, 0-72 h) exerts a direct effect on prostate cell growth through apoptosis[2]. Cell Viability Assay[2] Cell Line: WPMY-1, WPE1-NA22, BPH-1, LNCaP and VCaP Concentration: 1 nM-10 μM Incubation Time: WPMY-1 cells at 48 and 72h, WPE1-NA22 cells at 72 hours, BPH-1 cells at 48 and 72h, LNCaP cells at 48 and 72h Result: Reduced cell viability in all prostate cell lines, with the exception of the PC-3 cells. Apoptosis Analysis[2] Cell Line: WPE1-NA22, BPH-1, LNCaP and VCaP Concentration: 10 μM Incubation Time: 24, 48 and 72 h Result: Induced a significant increase on caspase 3/7 activation.

Degarelix (0-10 μg/kg; s.c.; once) decreases plasma LH levels and plasma testosterone levels in a dose-dependent manner in castrated rats[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]. Animal Model: Male Sprague-Dawley rats, castrated[3] Dosage: 0.3, 1, 3 and 10 μg/kg or 12.5, 50, and 200 μg/kg Administration: Subcutaneous injection, once Result: Produced a dose-dependent and reversible decrease in plasma LH levels with a minimal effective dose of 3 μg/kg. For the 50 μg/kg and 200 μg/kg doses, t1/2 of absorption values were 4 min and 30 min, Tmax values were 1 h and 5 h, and apparent plasma disappearance t1/2 values were 12 h and 67 h, respectively. Produced a dose-dependent decrease in plasma testosterone levels with a minimal effective dose of 1 μg/kg.

[1]. Rick FG, et al. An update on the use of degarelix in the treatment of advanced hormone-dependent prostate cancer. Onco Targets Ther. 2013 Apr 16;6:391-402.

[2]. Sakai M, et al. In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonistdegarelix on human prostate cell growth. PLoS One. 2015 Mar 26;10(3):e0120670.

[3]. Broqua P, et al. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormoneantagonist: degarelix. J Pharmacol Exp Ther. 2002 Apr;301(1):95-102.

[4]. Sonesson A, et al. Metabolite profiles of degarelix, a new gonadotropin-releasing hormone receptor antagonist, in rat, dog, and monkey. Drug Metab Dispos. 2011 Oct;39(10):1895-903.