Degarelix
(Synonyms: 地加瑞克) 目录号 : GC35828
A synthetic GNRHR antagonist
Cas No.:214766-78-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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)
| Cas No. | 214766-78-6 | SDF | |
| 别名 | 地加瑞克 | ||
| 分子式 | C82H103ClN18O16 | 分子量 | 1632.26 |
| 溶解度 | Water: 25 mg/mL (15.32 mM); DMSO: 10 mg/mL (6.13 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.6126 mL | 3.0632 mL | 6.1265 mL |
| 5 mM | 0.1225 mL | 0.6126 mL | 1.2253 mL |
| 10 mM | 0.0613 mL | 0.3063 mL | 0.6126 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Degarelix for treating advanced hormone-sensitive prostate cancer
Cochrane Database Syst Rev 2021 Aug 5;8(8):CD012548.PMID:34350976DOI:10.1002/14651858.CD012548.pub2.
Background: Degarelix is a gonadotropin-releasing hormone antagonist that leads to medical castration used to treat men with advanced or metastatic prostate cancer, or both. It is unclear how its effects compare to standard androgen suppression therapy. Objectives: To assess the effects of degree compared with standard androgen suppression therapy for men with advanced hormone-sensitive prostate cancer. Search methods: We searched multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science, LILACS until September 2020), trial registries (until October 2020), and conference proceedings (until December 2020). We identified other potentially eligible trials by reference checking, citation searching, and contacting study authors. Selection criteria: We included randomized controlled trials comparing Degarelix with standard androgen suppression therapy for men with advanced prostate cancer. Data collection and analysis: Three review authors independently classified studies and abstracted data from the included studies. The primary outcomes were overall survival and serious adverse events. Secondary outcomes were quality of life, cancer-specific survival, clinical progression, other adverse events, and biochemical progression. We used a random-effects model for meta-analyses and assessed the certainty of evidence for the main outcomes according to GRADE. Main results: We included 11 studies with a follow-up of between three and 14 months. We also identified five ongoing trials. Primary outcomes Data to evaluate overall survival were not available. Degarelix may result in little to no difference in serious adverse events compared to standard androgen suppression therapy (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.62 to 1.05; low-certainty evidence; 2750 participants). Based on 114 serious adverse events in the standard androgen suppression group, this corresponds to 23 fewer serious adverse events per 1000 participants (43 fewer to 6 more). We downgraded the certainty of evidence for study limitations and imprecision. Secondary outcomes Degarelix likely results in little to no difference in quality of life assessed with a variety of validated questionnaires (standardized mean difference 0.06 higher, 95% CI 0.05 lower to 0.18 higher; moderate-certainty evidence; 2887 participants), with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. Data to evaluate cancer-specific survival were not available. The effects of Degarelix on cardiovascular events are very uncertain (RR 0.15, 95% CI 0.04 to 0.61; very low-certainty evidence; 80 participants). We downgraded the certainty of evidence for study limitations, imprecision, and indirectness as this trial was conducted in a unique group of high-risk participants with pre-existing cardiovascular morbidities. Degarelix likely results in an increase in injection site pain (RR 15.68, 95% CI 7.41 to 33.17; moderate-certainty evidence; 2670 participants). Based on 30 participants per 1000 with injection site pain with standard androgen suppression therapy, this corresponds to 440 more injection site pains per 1000 participants (192 more to 965 more). We downgraded the certainty of evidence for study limitations. We did not identify any relevant subgroup differences for different Degarelix maintenance doses. Authors' conclusions: We did not find trial evidence for overall survival or cancer-specific survival comparing Degarelix to standard androgen suppression, but serious adverse events and quality of life may be similar between groups. The effects of Degarelix on cardiovascular events are very uncertain as the only eligible study had limitations, was small with few events, and was conducted in a high-risk population. Degarelix likely results in an increase in injection site pain compared to standard androgen suppression therapy. Maximum follow-up of included studies was 14 months, which is short. There is a need for methodologically better designed and executed studies with long-term follow-up evaluating men with metastatic prostate cancer.
Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial
Circulation 2021 Oct 19;144(16):1295-1307.PMID:34459214DOI:10.1161/CIRCULATIONAHA.121.056810.
Background: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. Methods: In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist Degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. Results: Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to Degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53). Conclusions: PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to Degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.
Questionable oncologic benefits of Degarelix
Urol Oncol 2016 Oct;34(10):423-6.PMID:27364704DOI:10.1016/j.urolonc.2016.05.029.
Introduction: Luteinizing hormone releasing hormone (LhRh) antagonist Degarelix has been approved by the Food and Drug Administration (FDA) for the treatment of advanced prostate cancer in 2008. However, the studies that followed such initial approval have several limitations. Objective: To make a critical review of those publications. Methods: Literature search on Degarelix. Results: The studies supporting the use of Degarelix are criticized on the basis of selection bias in regards to the heterogeneous populations described, ad hoc analyses with low statistical merit, and the presentation of selected data that would appear to be favorable to the evaluated medication. In addition, those studies still have not shown that any of the data that they point out have any association with clinical benefit. Conclusion: The flawed methodology of these publications makes the evidence to support the use of Degarelix rather weak.
The Efficacy and Safety of Relugolix Compared with Degarelix in Advanced Prostate Cancer Patients: A Network Meta-analysis of Randomized Trials
Eur Urol Oncol 2022 Apr;5(2):138-145.PMID:34301529DOI:10.1016/j.euo.2021.07.002.
Context: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. Objective: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus Degarelix. Evidence acquisition: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or Degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. Evidence synthesis: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of Degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and Degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, Degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and Degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, Degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and Degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. Conclusions: We found that the efficacy and safety of relugolix are comparable with those of Degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. Patient summary: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with Degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.
Degarelix
Drugs 2009 Oct 1;69(14):1967-76.PMID:19747011DOI:10.2165/10484080-000000000-00000.
Degarelix is a gonadotropin-releasing hormone (GnRH) receptor antagonist that, in common with GnRH receptor agonists (e.g. leuprolide, goserelin and triptorelin), is indicated for use as an androgen-deprivation therapy in patients with advanced prostate cancer. In 1-year, randomized, open-label, phase II or III trials in patients with all stages of prostate cancer, subcutaneous Degarelix was associated with rapid, profound and sustained suppression of serum testosterone and prostate-specific antigen (PSA), without evidence of testosterone surges or microsurges. In the phase III trial, Degarelix (240 mg initially followed by 80 mg every 28 days) was considered to be effective and noninferior to intramuscular leuprolide (7.5 mg every 28 days) with regard to inducing and maintaining suppression of serum testosterone to castrate levels (i.e.