Abarelix (acetate)
(Synonyms: 阿巴瑞克乙酸盐; PPI 149 Acetate; R 3827 Acetate) 目录号 : GC45778
A synthetic GnRHR antagonist
Cas No.:785804-17-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Abarelix is a synthetic third generation gonadotropin-releasing hormone receptor (GnRHR) antagonist (IC50 = 3.5 nM in HEK293 cells expressing the human receptor).1,2 It increases histamine release from rat peritoneal mast cells in vitro and from a human skin model ex vivo.3,4 In vivo, abarelix (200 μg/kg) decreases plasma luteinizing hormone (LH) levels six hours post-treatment in castrated rats, with levels returning to baseline within 24 hours.3 Abarelix (2 mg/kg) also transiently decreases plasma testosterone levels in intact rats, with levels returning to baseline within seven days post-treatment. Formulations containing abarelix have previously been used in the treatment of advanced prostate cancer.
|1. Tan, O., and Bukulmez, O. Biochemistry, molecular biology and cell biology of gonadotropin-releasing hormone antagonists. Curr. Opin. Obstet. Gynecol. 23(4), 238-244 (2011).|2. 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 6. J. Med. Chem. 44(3), 453-467 (2001).|3. Broqua, P., Riviere, P.J.-M., Conn, P.M., et al. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: Degarelix. J. Pharmacol. Exp. Ther. 301(1), 95-102 (2002).|4. Koechling, W., Hjortkjaer, R., and TankÓ, L.B. 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. 70(4), 580-587 (2010).
| Cas No. | 785804-17-3 | SDF | |
| 别名 | 阿巴瑞克乙酸盐; PPI 149 Acetate; R 3827 Acetate | ||
| Canonical SMILES | CC(N[C@H](CC1=CC(C=CC=C2)=C2C=C1)C(N[C@H](CC3=CC=C(Cl)C=C3)C(N[C@H](CC4=CC=CN=C4)C(N[C@@H](CO)C(N(C)[C@@H](CC5=CC=C(O)C=C5)C(N[C@H](CC(N)=O)C(N[C@@H](CC(C)C)C(N[C@@H](CCCCNC(C)C)C(N6CCC[C@H]6C(N[C@H](C)C(N)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O.OC(C)=O | ||
| 分子式 | C72H95ClN14O14.XC2H4O2 | 分子量 | 1416.1 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,PBS (pH 7.2): 5 mg/ml | 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 | 3.5308 mL | 7.0616 mL |
| 5 mM | 0.1412 mL | 0.7062 mL | 1.4123 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。
A phase 3, multicenter, open-label, randomized study of Abarelix versus leuprolide acetate in men with prostate cancer
Urology 2001 Nov;58(5):756-61.PMID:11711355DOI:10.1016/s0090-4295(01)01342-5.
Objectives: To evaluate the levels of testosterone and other hormones in men with prostate cancer treated with Abarelix versus leuprolide acetate. Methods: Patients (n = 269) were randomized to receive open-label Abarelix 100 mg or leuprolide acetate 7.5 mg by intramuscular injection. The results of the first 84 days of the study are reported. The primary efficacy endpoints included avoidance of testosterone surge, castration on day 8, and achievement and maintenance of castration from days 29 through 85. The secondary endpoints included castration on days 2, 4, and 15; a reduction in prostate-specific antigen level; and measurements of other hormones. Patients were monitored for clinical adverse events and laboratory abnormalities. Results: No men in the Abarelix group and 82% of men in the leuprolide acetate group experienced a testosterone surge (P <0.001). Abarelix caused rapid medical castration: 24% of men 1 day after treatment and 78% after 7 days compared with 0% of men treated with leuprolide acetate on either day. A comparable percentage of men achieved and maintained castration between days 29 and 85 in each group. Prostate-specific antigen had a statistically significant decrease for the first month in patients treated with Abarelix. Dihydrotestosterone, luteinizing hormone, prostate-specific antigen, and follicle-stimulating hormone showed similar rapid reductions without an initial increase. The overall occurrence of adverse events was similar across the treatment groups, and most were sequelae of comorbid disorders. Conclusions: Treatment with Abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, luteinizing hormone, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.
A phase 3, multicenter, open label, randomized study of Abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer
J Urol 2002 Apr;167(4):1670-4.PMID:11912385DOI:10.1097/00005392-200204000-00021.
Purpose: We compared the endocrinological and biochemical efficacy of Abarelix depot, a gonadotropin-releasing hormone antagonist, with that of a widely used combination of luteinizing hormone releasing hormone agonist and a nonsteroidal antiandrogen. Materials and methods: A total of 255 patients were randomized to receive open label 100 mg. Abarelix depot or 7.5 mg. leuprolide acetate intramuscularly injection on days 1, 29, 57, 85, 113 and 141 for 24 weeks. Patients in the Abarelix group received an additional injection on day 15 and those in the leuprolide acetate group received 50 mg. bicalutamide daily. Patients could continue treatment with study drug for an additional 28 weeks. The efficacy end points were the comparative rates of avoidance of testosterone surge (greater than 10% increase) within 7 days of the first injection and the rapidity of achieving reduction of serum testosterone to castrate levels (50 ng./dl. or less) on day 8. Patients were monitored for adverse events and laboratory abnormalities. Results: Abarelix was more effective in avoidance of testosterone surge (p <0.001) and the rapidity of reduction of testosterone to castrate levels on day 8 (p <0.001) than combination therapy. No significant difference was seen between the groups in the initial rate of decline of serum prostate specific antigen or the ability to achieve and maintain castrate levels of testosterone. No unusual or unexpected adverse events were reported. Conclusions: Abarelix as monotherapy achieves medical castration significantly more rapidly than combination therapy and avoids the testosterone surge characteristic of agonist therapy. Both treatments were equally effective in reducing serum prostate specific antigen, and achieving and maintaining castrate levels of testosterone.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2002 May;24(4):217-48.PMID:12092009doi
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, Abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole hydrochloride, rosuvastatin calcium; Sevoflurane, sildenafil citrate, simvastatin, somatropin; Tacrolimus, tamoxifen citrate, telmisartan, temozolomide, thiopental sodium, tinzaparin sodium, tirofiban hydrochloride, treosulfan, triamcinolone acetonide; Urokinase; Valsartan, vardenafil, vincristine; Warfarin sodium; Ximelagatran; Zidovudine.
The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters
J Urol 2006 Aug;176(2):520-5.PMID:16813881DOI:10.1016/j.juro.2006.03.057.
Purpose: Although prostate cancer specific mortality is decreasing, there is little effect on overall mortality in this population, suggesting the possibility of an increased risk of death from nonprostate cancer related causes. Androgen deprivation therapy could adversely affect cardiovascular health. We investigated changes in lipid and glucose during androgen deprivation therapy. Materials and methods: We performed an exploratory analysis of pooled data from 3 prospective clinical trials aimed at achieving medical castration by comparing the gonadotropin releasing hormone antagonist Abarelix, the gonadotropin releasing hormone agonist leuprolide acetate and leuprolide acetate plus the antiandrogen bicalutamide. Most patients were treated in the neoadjuvant setting or because of biochemical recurrence. Fasting serum lipid, glucose and hemoglobin A1C were determined in 1,102 men at baseline, and on treatment days 85 and 169. In the current study men were categorized into 3 treatment groups according to the type of androgen deprivation therapy, that is leuprolide acetate, leuprolide acetate plus bicalutamide or Abarelix, and statin therapy. Results: Significant increases in total cholesterol, triglyceride and high density lipoprotein-cholesterol were observed in patients on leuprolide acetate or Abarelix but not in patients on leuprolide acetate plus bicalutamide. Consistent changes in low density lipoprotein-cholesterol were not detected. Increased total cholesterol was usually due to an increase in high density lipoprotein-cholesterol. Hemoglobin A1C increased from baseline to day 85 only and there were no significant changes in fasting glucose measurements. The type of androgen deprivation therapy did not affect these parameters. Conclusions: Short-term androgen deprivation therapy affects serum lipid and hemoglobin A1C independent of statin therapy.
Utility of LHRH antagonists for advanced prostate cancer
Can J Urol 2014 Apr;21(2 Supp 1):22-7.PMID:24775720doi
Introduction: Androgen deprivation therapy (ADT) is the lynchpin of treatment for advanced prostate cancer. Prescribing physicians and patients have a choice between orchiectomy, luteinizing hormone releasing hormone (LHRH) agonists, combined androgen deprivation (CAD) or LHRH antagonists. Materials and methods: Literature relating to the use of LHRH antagonists in the management of prostate cancer was reviewed. Results: Abarelix was the first-in-class LHRH pure antagonist that was Food and Drug Administration (FDA) approved in 2003. Due to a variety of concerns including hypersensitivity reactions it was withdrawn from the United States (U.S.) market in 2005. The only currently commercially available LHRH antagonist in the U.S. is degarelix available as a once-a-month depot injection. The potential clinical advantage of degarelix compared to the LHRH agonists is the very rapid and sustained testosterone suppression with no identifiable physiological or clinical testosterone surge or flare. The main disadvantage of degarelix compared to the LHRH agonists is the monthly dosing and the inconvenience for some patients and practices. Recent studies tout improved disease control for degarelix compared to monthly leuprolide acetate; however, these results remain controversial. Conclusions: The rapid T-suppression achieved with degarelix may provide a clinical benefit for various groups of men with advanced or locally advanced disease.