Firibastat
(Synonyms: QGC001; RB150) 目录号 : GC62113
Firibastat (QGC001) 是一种口服活性的 EC33 前体药物。Firibastat 是一种首创的脑氨基肽酶 A (APA) 抑制剂 (Ki=200 nM)，选择性和特异性地抑制高血压大鼠脑血管紧张素 II 转化为血管紧张素 III，并降低血压。
Cas No.:648927-86-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Firibastat (QGC001), an orally active brain penetrating prodrug of EC33, is a first-in-class brain aminopeptidase A (APA) inhibitor (Ki=200 nM). Firibastat selectively and specifically inhibits conversion of brain angiotensin-II into angiotensin-III and decreases blood pressure in hypertensive rats[1][2].
When given orally, Firibastat (0.1-30 mg/kg; p.o.) crosses the gastrointestinal and blood-brain barriers, enters the brain, and generates two active molecules of EC33 which inhibit brain APA activity, blocking brain angiotensin III formation, and decrease blood pressure for several hours in hypertensive rats[2].
[1]. Ferdinand KC, et al. Efficacy and Safety of Firibastat, A First-in-Class Brain Aminopeptidase A Inhibitor, in Hypertensive Overweight Patients of Multiple Ethnic Origins. Circulation. 2019;140(2):138-146.
[2]. Keck M, et al. Orally Active Aminopeptidase A Inhibitor Prodrugs: Current State and Future Directions. Curr Hypertens Rep. 2019;21(7):50. Published 2019 May 21.
| Cas No. | 648927-86-0 | SDF | |
| 别名 | QGC001; RB150 | ||
| 分子式 | C8H20N2O6S4 | 分子量 | 368.51 |
| 溶解度 | Water : 41.67 mg/mL (113.08 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.7136 mL | 13.5682 mL | 27.1363 mL |
| 5 mM | 0.5427 mL | 2.7136 mL | 5.4273 mL |
| 10 mM | 0.2714 mL | 1.3568 mL | 2.7136 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。
Firibastat: a Novel Treatment for Hypertension
Curr Hypertens Rep 2021 Dec 24;23(12):46.PMID:34950965DOI:10.1007/s11906-021-01163-4.
Purpose of review: The purpose of this review is to discuss the unique mechanism of Firibastat, a new antihypertension medication. Hypertension continues to be a highly prevalent public health issue. Recent findings: Firibastat is a novel agent developed to treat hypertension. As the first member in the class of centrally acting agents to target the brain renin angiotensin system, Firibastat offers new pathways to consider and enhances the regimen of agents currently available to treat hypertension. Recent clinical trials have demonstrated effectiveness and safety in mild hypertension as well as resistant hypertension. This review introduces Firibastat as a new therapeutic class of treatment for hypertension focused on the renin angiotensin system in the brain. Early studies have shown a significant reduction in blood pressure with minimal side effects particularly in patients who are difficult to treat.
Firibastat: A Novel Brain Aminopeptidase Inhibitor - A New Era of Antihypertensive therapy
Curr Probl Cardiol 2022 Sep;47(9):100859.PMID:33994025DOI:10.1016/j.cpcardiol.2021.100859.
Global incidence and prevalence of hypertension continues to increase and remains a significant challenge. The ever-increasing number of cases are due to comorbid conditions such as obesity and diabetes, as well as lifestyle indiscretions such as excessive salt intake. Hypertension, congestive heart failure, and kidney disease are all conditions resulting from abnormal Renin-Angiotensin-Aldosterone activation and adverse remodeling. Firibastat, a novel Brain Aminopeptidase inhibitor, may be able to help achieve blood pressure control in those with resistant hypertension. In this review article, we will discuss the biochemical pathway of Firibastat and various trials assessing drug efficacy in animals and humans. This drug has the potential to curb the risk of uncontrolled hypertension and help improve long term cardiovascular morbidity and mortality.
Current Knowledge about the New Drug Firibastat in Arterial Hypertension
Int J Mol Sci 2022 Jan 27;23(3):1459.PMID:35163378DOI:10.3390/ijms23031459.
Hypertension significantly increases the risk of cardiovascular disease. Currently, effective standard pharmacological treatment is available in the form of diuretics, ACE inhibitors, angiotensin II receptor blockers and calcium channel blockers. These all help to decrease blood pressure in hypertensive patients, each with their own mechanism. Recently, Firibastat, a new first-in-class antihypertensive drug has been developed. Firibastat is a prodrug that when crossing the blood-brain barrier, is cleaved into two active EC33 molecules. EC33 is the active molecule that inhibits the enzyme aminopeptidase A. Aminopeptidase A converts angiotensin II to angiotensin III. Angiotensin III usually has three central mechanisms that increase blood pressure, so by inhibiting this enzyme activity, a decrease in blood pressure is seen. Firibastat is an antihypertensive drug that affects the brain renin angiotensin system by inhibiting aminopeptidase A. Clinical trials with Firibastat have been performed in animals and humans. No severe adverse effects related to Firibastat treatment have been reported. Results from studies show that Firibastat is generally well tolerated and safe to use in hypertensive patients. The aim of this review is to investigate the current knowledge about Firibastat in the treatment of hypertension.
Firibastat: An Oral First-in-Class Brain Aminopeptidase A Inhibitor for Systemic Hypertension
Cardiol Rev 2022 Jan-Feb;30(1):50-55.PMID:33027067DOI:10.1097/CRD.0000000000000360.
Systemic hypertension is the leading cause of death and disability worldwide. The management of hypertension is challenging in the high-risk patient population with high salt-sensitivity and low serum renin levels. The renin-angiotensin system (RAS) plays a central role in blood pressure (BP) regulation. While we have effective medications to act on peripheral RAS, our understanding of brain RAS and its effect on BP regulation is still in an evolving stage. Brain RAS hyperactivity is associated with the development and maintenance of hypertension. In comparison to peripheral RAS, where angiotensin II is the most crucial component responsible for BP regulation, angiotensin III is likely the main active peptide in the brain RAS. Angiotensin II is metabolized by aminopeptidase A into angiotensin III in the brain. EC33 is a potent inhibitor of brain aminopeptidase A tested in animal models. The use of EC33 in conscious spontaneously hypertensive rats, hypertensive deoxycorticosterone acetate-salt rats, and conscious normotensive rat models leads to a reduction in BP. In order to facilitate the passage of EC33 through the blood-brain barrier, the 2 molecules of EC33 were linked by a disulfide bridge to form a prodrug called RB150. RB150, later renamed as QGC001 or Firibastat, was found to be effective in animal models and well-tolerated when used in healthy participants. Firibastat was found to be safe and effective in phase 2 trials, and is now planned to undergo a phase 3 trial. Firibastat has the potential to be groundbreaking in the management of resistant hypertension.
Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: A review of clinical trials
Avicenna J Med 2021 Jan 5;11(1):1-7.PMID:33520782DOI:10.4103/ajm.ajm_117_20.
An unfortunate subset of hypertensive patients develops resistant hypertension in which optimal doses of three or more first-line antihypertensive drugs fail to sufficiently control blood pressure. Patients with resistant hypertension represent a high-risk and difficult-to-treat group, and such patients are at amplified jeopardies for substantial hypertension-related multi-organ failure, morbidity, and mortality. Thus, there is a pressing requirement to better improve blood pressure control through the pharmaceutical generation of novel classes of antihypertensive drugs that act on newer and alternative therapeutic targets. The hyperactivity of the brain renin-angiotensin system (RAS) has been shown to play a role in the pathogenesis of hypertension in various experimental and genetic hypertensive animal models. In the brain, angiotensin-II is metabolized to angiotensin-III by aminopeptidase A (APA), a membrane-bound zinc metalloprotease enzyme. A large body of evidence has previously established that angiotensin-III is one of the main effector peptides of the brain RAS. Angiotensin-III exerts central stimulatory regulation over blood pressure through several proposed mechanisms. Accumulating evidence from preclinical studies demonstrated that the centrally acting APA inhibitor prodrugs (Firibastat and NI956) are very safe and effective at reducing blood pressure in various hypertensive animal models. The primary purpose of this study is to narratively review the published phase I-II literature on the safety and efficacy of APA inhibitors in the management of patients with hypertension. Moreover, a summary of ongoing clinical trials and future perspectives are presented.