214766-78-6
214766-78-6 結(jié)構(gòu)式
基本信息
醋酸地加瑞克
DEGARELIX
Degarelix acetate
Degarelix impurity
DEGARELIX USP/EP/BP
Degarelix acetate salt
Degarelix, Degarelix acetate
Degarelix acetate(FE-200486,Degarelix)
N-Acetyl-3-(2-naphthyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridyl)-D-alanyl-L-seryl-4-[2,6-dioxohexahydropyrimidin-4(S)-ylcarboxamido]-L-phenylalanyl-4-ureido-D-phenylalanyl-L-leucyl-N6-isopropyl-L-lysyl-L-prolyl-D-alaninamide acetate
D-Alaninamide,N-acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-4-[[[(4S)-hexahydro-2,6-dioxo-4-pyrimidinyl]carbonyl]amino]-L-phenylalanyl-4-[(aminocarbonyl)amino]-D-phenylalanyl-L-leucyl-N6-(1-methylethyl)-L-ly
物理化學性質(zhì)
H2O:25.0(Max Conc. mg/mL);15.32(Max Conc. mM)
常見問題列表
醋酸地加瑞克是一種合成的促性腺激素釋放激素（GnRH）受體拮抗劑，通過與腦下垂體的GnRH受體可逆的結(jié)合，減少促性腺激素及睪酮的釋放，從而發(fā)揮抗前列腺癌作用。
地加瑞克（商品名：費蒙格®）是最新一代的GnRH拮抗劑，在其分子的5，6位并入了P-尿基苯丙氨酸，化學結(jié)構(gòu)的改變使得藥物作用時間延長的同時避免了因組胺釋放引起的超敏反應。
地加瑞克的臨床有效性、安全性和長期用藥均得到了多個臨床驗證，是目前應用最廣泛的GnRH拮抗劑。對于晚期前列腺癌骨轉(zhuǎn)移，地加瑞克同樣表現(xiàn)出良好的優(yōu)越性，有研究顯示前列腺癌骨轉(zhuǎn)移患者通過地加瑞克治療1年后，較GnRH激動劑治療顯著降低了血漿堿性磷酸酶（S-ALP），而S-ALP往往升高往往與骨轉(zhuǎn)移相關。
2018年11月我國國家藥品監(jiān)督管理局（NMPA）批準地加瑞克上市，用于雄激素依賴的前列腺癌患者，對于我國前列腺癌患者來說無疑又是一項重大利好。
地加瑞克是丹麥輝凌制藥有限公司研發(fā)的促性腺激素釋放激素(GnRH)受體抑制劑類藥物，可逆性抑制垂體GnRH受體來減少促性腺激素釋放繼而抑制睪酮的釋放。地加瑞克通過抑制對前列腺癌持續(xù)生長至關重要的睪酮來延緩前列腺癌的生長和惡化。以激素治療前列腺癌來降低睪酮濃度的初期卻造成睪酮濃度激增，此初始刺激該激素受體可暫時性促進腫瘤生長而不是抑制它，而地加瑞克則不會。
醋酸地加瑞克是一種促性腺激素釋放激素受體阻滯劑，該藥已分別在美國和歐美被批準用于晚期(激素依賴的)前列腺癌治療，在日本被批準用于前列腺癌治療。
GnRHR
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. 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.
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. 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%).