Abarelix (R3827)
(Synonyms: 阿巴瑞克; R3827; PPI 149) 目录号 : GC32843
Abarelix (R3827) (R3827; PPI 149) 是一种有效的促性腺激素释放激素 (GnRH) 拮抗剂，用于治疗前列腺癌。
Cas No.:183552-38-7
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
Abarelix is a potent gonadotrophin-releasing hormone (GnRH) antagonist, used for prostate cancer treatment.
Abarelix (30 and 300 µg/mL) and cetrorelix cause significantly increased histamine release[1]. Abarelix is the firstGnRH antagonist to be developed, and can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term[2]. Abarelix demonstrates to promptly and substantially reduce follicle-stimulating hormone levels to lower than LHRH agonist. Abarelix does not cause a surge in serum testosterone that can precipitate a flare phenomenon or worsening of disease, particularly dangerous for patients with metastatic, symptomatic disease, and produces medical castration more quickly[3].
[1]. Koechling W, et al. Degarelix, a novel GnRH antagonist, causes minimal histamine release compared with cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples. Br J Clin Pharmacol. 2010 Oct;70(4):580-7. [2]. Kirby RS, et al. Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. BJU Int. 2009 Dec;104(11):1580-4. [3]. Debruyne F, et al. Abarelix for injectable suspension: first-in-class gonadotropin-releasing hormone antagonist for prostate cancer. Future Oncol. 2006 Dec;2(6):677-96.
| Cas No. | 183552-38-7 | SDF | |
| 别名 | 阿巴瑞克; R3827; PPI 149 | ||
| Canonical SMILES | Ac-{d-2-Nal}-{d-4-Cpa}-{d-3-Pal}-Ser-{NMeTyr}-{d-Asp}-Leu-Lys(ipr)-Pro-{d-Ala}-NH2 | ||
| 分子式 | C72H95ClN14O14 | 分子量 | 1416.06 |
| 溶解度 | DMSO : ≥ 14.2 mg/mL (10.03 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 | 0.7062 mL | 3.5309 mL | 7.0618 mL |
| 5 mM | 0.1412 mL | 0.7062 mL | 1.4124 mL |
| 10 mM | 0.0706 mL | 0.3531 mL | 0.7062 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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。
Abarelix for injectable suspension: first-in-class gonadotropin-releasing hormone antagonist for prostate cancer
Future Oncol 2006 Dec;2(6):677-96.PMID:17155895DOI:10.2217/14796694.2.6.677.
Abarelix, a gonadotropin-releasing hormone antagonist, with its indication for advanced symptomatic prostate cancer, represents the newest category of hormonal therapy introduced in the past 15 years. Results from Phase II and III clinical trials demonstrate the advantages of Abarelix over commonly used luteinizing hormone-releasing hormone (LHRH) agonist therapy: Abarelix does not cause a surge in serum testosterone that can precipitate a flare phenomenon or worsening of disease, particularly dangerous for patients with metastatic, symptomatic disease, and produces medical castration more quickly. Abarelix was also demonstrated to promptly and substantially reduce follicle-stimulating hormone levels to lower than LHRH agonist. Study results demonstrate effective anticancer responses during extended exposure to Abarelix: improvements in pain score and/or analgesic use, improvements in urinary symptoms (including urinary catheter removal) and complete avoidance of bilateral orchiectomy for patients undergoing at least 12 weeks of treatment. In Phase III clinical trials, Abarelix demonstrated a similar overall safety profile when compared with LHRH agonist monotherapy, and a superior safety profile when compared with LHRH agonist plus antiandrogen combination therapy. Abarelix patients experienced a greater incidence of immediate-onset systemic allergic reactions as compared with control arms.
Abarelix: abarelix-depot-F, abarelix-depot-M, abarelix-L, PPI 149, R 3827
Drugs R D 2003;4(3):161-6.PMID:12757402DOI:10.2165/00126839-200304030-00004.
Abarelix [Abarelix-Depot-F, Abarelix-Depot-M, Abarelix-L, PPI 149, R 3827, Plenaxis] is a peptide consisting of natural and artificial amino acids. In females, Abarelix is an estrogen production antagonist with potential for the treatment of breast cancer, endometriosis and other reproductive hormone diseases. In males it is a testosterone production antagonist and has potential as hormonal therapy of prostate cancer. Depot formulations of Abarelix (abarelix-depot-M and abarelix-depot-F) are being developed for hormonally responsive prostate cancer and endometriosis, respectively. Clinical development of the depot formulations is currently being conducted by Praecis Pharmaceuticals, the originators of the agent. A non-depot formulation, abarelix-L, was also being conducted for prostate gland volume reduction. Praecis Pharmaceuticals has entered into a number of licensing agreements covering Abarelix. However, all agreements have since been terminated leaving Praecis to develop and commercialise the agent on its own. The terminated agreements include an agreement between Praecis and Roche for the commercialisation of Abarelix in the US. This agreement was terminated in November 1998. Praecis Pharmaceuticals also entered into a collaborative agreement with Amgen in March 1999, whereby the companies would develop Abarelix and Amgen would commercialise the drug in the US, Canada, Australia, Asia and several secondary markets. However, in September 2001, Praecis and Amgen announced that they were terminating the agreement for all indications. Praecis stated at the time that it remained committed to developing Abarelix for both prostate cancer and endometriosis. Amgen had submitted 'Lotestrol' to the US Patent and Trademarks Office as a possible tradename for abarelix-depot-M. Lotestrol may also have been under consideration as a tradename for abarelix-depot-F. Praecis had also sold European, African, Latin American and Middle Eastern rights to Abarelix to Sanofi-Synthélabo. However, in October 2001, Sanofi-Synthélabo announced that it had waived its rights to Abarelix. Praecis confirmed in December 2000 that it had filed an NDA seeking FDA approval for Abarelix in the US. In January 2001, the FDA granted the Abarelix application priority review status. However, in June 2001, the FDA rejected the NDA for prostate cancer. The FDA requested that Praecis use existing data from the completed trials to analyse the allergic reactions that occurred in a small subset of patients. The FDA also expressed concerns over the lack of maintenance of testosterone suppression beyond the 3-month timeframe that occurred in a subset of patients. In February 2003, Praecis announced the re-submission of its NDA to the US FDA. The submission seeks approval for the use of Abarelix in a defined subpopulation of advanced prostate cancer patients for whom the current hormonal therapies are not appropriate. Praecis plans to submit its regulatory application in Europe during the second quarter of 2003. Following the completion of a phase I/II trial of abarelix-L in prostate gland volume reduction, a phase IIIb study of the depot formulation was initiated in September 2001. The trial is comparing the effects of neoadjuvant hormonal therapy with depot formulations of leuprorelin or Abarelix for prostate gland volume reduction. Abarelix-L is no longer mentioned on Praecis' website, suggesting that development of this formulation is no longer being pursued. The Financial Times (ft.com) reported in May 2001 that approximately 12 new anti-cancer agents are expected to be approved by the FDA through to the end of 2002, with the potential to generate total sales of US dollars 2.6 billion--abarelix is one of these products. The paper quoted analysts at Salomon Smith Barney predicting that Abarelix could reach sales of US dollars 120 million for the indication of prostate cancer. However, in June 2001 the FDA rejected Praecis Pharmaceuticale FDA rejected Praecis Pharmaceuticals' NDA filing; this was later re-submitted in February 2003. A year earlier, in May 2000, the Financial Times (ft.com) stated that Credit Suisse First Boston had forecast Abarelix to reach peak sales of 1 billion US dollars . Other analysts, at SG Cowen, predicted annual sales of US dollars 200 million for the first 3 years; however, this could increase to 1 billion US dollars if Abarelix is also approved for the indication of endometriosis. Abarelix' main competitors at the time were said to be Lupron [TAP Pharmaceuticals], Viadur [Alza] and Zoladex [AstraZeneca].
Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer
BJU Int 2009 Dec;104(11):1580-4.PMID:20053189DOI:10.1111/j.1464-410X.2009.08924.x.
Hormonal therapy is the main recommended treatment for locally advanced and metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH) agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately leading to its de-sensitization and subsequent reduction of LH and testosterone levels. However, this reduction is accompanied by a well described increase or 'surge' in LH and testosterone levels, necessitating the concomitant administration of an antiandrogen to combat the potential effects of transient acceleration in cancer activity. Two pure GnRH antagonists have been developed, Abarelix and degarelix, that are devoid of any agonist effect on the GnRH receptor and consequently do not result in testosterone flare. Abarelix was the first GnRH antagonist to be developed and was approved by the USA Food and Drug Administration in 2004 for the initiation of hormonal castration in advanced or metastasizing hormone-dependent prostate carcinoma, when rapid androgen suppression is necessary. Clinical data on both Abarelix and degarelix show that they can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term.
Abarelix: the first gonadotrophin-releasing hormone antagonist for the treatment of prostate cancer
Expert Opin Pharmacother 2004 Oct;5(10):2171-9.PMID:15461552DOI:10.1517/14656566.5.10.2171.
The high incidence of prostate cancer makes it a major healthcare problem and the second leading cancer-related cause of death among men in developed countries. The hormonal treatment of prostate cancer is indicated for the palliation of symptomatic and metastatic disease in older patients, and as neoadjuvant treatment of different modalities of radiotherapy. This hormonal treatment is based on the study conducted by Huggins in 1940 and consists of androgen suppression. Since the clinical availability of the first luteinising hormone-releasing hormone (LHRH) agonist, no significant improvement has been made in the field of medical castration. Taking these data into consideration, the recent approval of Abarelix by the FDA, the first gonadotrophin-releasing hormone (GnRH) antagonist, appears to be promising news. The pharmacology of the molecule and the clinical studies that led to FDA approval will be reviewed. The place of GnRH antagonists in the treatment modalities of prostate cancer will then be discussed.
Technology evaluation: Abarelix, Praecis pharmaceuticals
Curr Opin Mol Ther 2000 Oct;2(5):579-85.PMID:11249760doi
Abarelix (PPI-149) is a luteinizing hormone-releasing hormone (LHRH) receptor antagonist under development by Praecis, Amgen and Sanofi-Synthelabo for the potential treatment of prostate cancer, breast cancer and hormone-related disorders [285672,328910]. Abarelix has entered phase III clinical trials for hormonally responsive prostate cancer [311887], and a sustained-release formulation is in a phase I/II clinical trial for endometriosis [317822]. In June 1997, Praecis entered into a collaboration with Sanofi-Synthelabo for the continued development and future marketing of Abarelix for the treatment of prostate cancer and other hormone-related disorders in Europe [248307]. In June 1998, Roche gained marketing rights in the US and elsewhere, under a joint development agreement [289677], which was later terminated. In March 1999, Amgen gained rights to develop Abarelix in the US, Canada, Australia, Asia and other secondary markets [317822]. Sanofi-Synthelabo expects to launch the compound in Europe in 2001 [345341,346302]. In March 1999, Merrill Lynch predicted sales in 2001 of US$75 million, with peak sales of up to US$400 million [336561]. In October 1999, Merrill Lynch predicted sales in 2003 of EUR 100 million [346209] and Lehman Brothers predicted sales of US$50 million in 2002 rising to a peak of US$150 million in 2010 [346267].