Berotralstat
(Synonyms: BCX7353) 目录号 : GC62865
Berotralstat (BCX7353) 是一种低毒性，有效，高特异性，第二代，具有口服活性的 plasma kallikrein 抑制剂，用于遗传性血管水肿 (hereditary angioedema，HAE) 的研究。 Berotralstat 通过阻断 plasma kallikrein 释放缓激肽的酶活性来发挥作用，缓激肽是促进与 HAE 发作相关的肿胀和疼痛的主要生物肽。
Cas No.:1809010-50-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Berotralstat (BCX7353) is a low toxicity, effective, highly specific, second-generation, synthetic and orally active plasma kallikrein inhibitor used for the research of hereditary angioedema (HAE) attacks. Berotralstat works by blocking the enzymatic activity of plasma kallikrein in releasing bradykinin, the major biologic peptide that promotes swelling and pain associated with attacks of HAE[1][2].
[1]. Zuraw B, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial [published online ahead of print, 2020 Oct 21]. J Allergy Clin Immunol. 2020;S0091-6749(20)31484-6.
[2]. Manning ME, et al. Berotralstat (BCX7353) is a novel oral prophylactic treatment for hereditary angioedema: Review of phase II and III studies. Allergy Asthma Proc. 2021;42(4):274-282.
| Cas No. | 1809010-50-1 | SDF | |
| 别名 | BCX7353 | ||
| 分子式 | C30H26F4N6O | 分子量 | 562.56 |
| 溶解度 | 储存条件 | ||
| 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 | 1.7776 mL | 8.8879 mL | 17.7759 mL |
| 5 mM | 0.3555 mL | 1.7776 mL | 3.5552 mL |
| 10 mM | 0.1778 mL | 0.8888 mL | 1.7776 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。
Berotralstat: First Approval
Drugs 2021 Feb;81(3):405-409.PMID:33646555DOI:10.1007/s40265-021-01475-4.
Berotralstat (ORLADEYO™) is an orally administered kallikrein inhibitor, which has been developed by BioCryst Pharmaceuticals for hereditary angioedema (HAE). The inhibition of kallikrein by Berotralstat decreases the production of bradykinin, which prevents the localised tissue oedema that occurs during attacks of HAE. Berotralstat has been approved in the USA, and subsequently in Japan, for prophylaxis to prevent attacks of HAE in adults and paediatric patients aged 12 years or older. This article summarises the milestones in the development of Berotralstat leading to this first approval for prophylaxis to prevent attacks of HAE.
Orladeyo (Berotralstat): A Novel Oral Therapy for the Prevention of Hereditary Angioedema
Ann Pharmacother 2022 Apr;56(4):488-493.PMID:34282650DOI:10.1177/10600280211032982.
Objective: The purpose of this article is to review the available trials that led to the Food and Drug Administration (FDA) approval of Berotralstat, an oral kallikrein inhibitor, for the prevention of hereditary angioedema (HAE) attacks. Data sources: PubMed and ClincalTrials.gov were searched using key term Berotralstat to identify phase III clinical trials related to the FDA approval of Berotralstat from April 2018 to May 2021. Study selection and data extraction: Trials selected were those that influenced the FDA approval of Berotralstat or provided novel information regarding the safety and efficacy of this therapy in the treatment of HAE. Data synthesis: Both APeX-2 and ApeX-J found clinically significant benefit with Berotralstat 150 mg daily for reduction in HAE attacks when compared with placebo (1.31 vs 2.35, P < 0.001, and 1.11 vs 2.18, P < 0.001, attacks in the APeX-2 and APeX-J trials, respectively). APeX-2 also showed a statistically significant benefit for Berotralstat 110 mg daily (1.65 vs 2.35 attacks [1.65 attacks, P = 0.024]). Relevance to patient care and clinical practice: An advantage Berotralstat has over the other approved therapies is that it is administered orally, which may garner patient preference because of ease of administration. Berotralstat has also shown a potential benefit in reducing the need for standard-of-care treatment for HAE attacks, which has not been studied with alternative agents. Conclusions: Berotralstat 150 mg daily has been proven safe and effective in clinical studies and appears to be a viable oral alternative to parenteral medications currently used in HAE prophylaxis.
Oral once-daily Berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial
J Allergy Clin Immunol 2021 Jul;148(1):164-172.e9.PMID:33098856DOI:10.1016/j.jaci.2020.10.015.
Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. Objective: Our aim was to determine the efficacy, safety, and tolerability of Berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily Berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of Berotralstat, 150-mg of dose Berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with Berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. Conclusion: Both the 110-mg and 150-mg doses of Berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
Berotralstat (BCX7353) is a novel oral prophylactic treatment for hereditary angioedema: Review of phase II and III studies
Allergy Asthma Proc 2021 Jul 14;42(4):274-282.PMID:34127176DOI:10.2500/aap.2021.42.210034.
Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable and potentially life-threatening episodes of swelling in various parts of the body. These attacks can be painful and debilitating, and affect a patient's quality of life. Every patient who experiences an attack should be treated with on-demand medication to mitigate attack severity and duration. Many patients with HAE also receive long-term prophylaxis to reduce the frequency and severity of edema episodes. Although long-term prophylaxis reduces the disease burden for patients with HAE, available intravenous and subcutaneous treatments are accompanied by a significant treatment burden because of the logistical, emotional, and physical challenges posed by their long-term parenteral nature. Androgens are an effective oral prophylactic treatment; however, they are associated with significant adverse events and are not suitable for all patients. Thus, the HAE community has expressed interest in the development of alternative oral prophylactic therapies for preventing HAE attacks. Objective: Here, we review the phase II and III clinical data of Berotralstat (BCX7353), which was approved by the U.S. Food and Drug Administration in December 2020. Results: Berotralstat is an oral, second-generation, synthetic, small-molecule plasma kallikrein inhibitor taken once daily for the prevention of HAE attacks in patients ages ≥ 12 years. Results from the APeX studies (APeX-1 NCT02870972, APeX-2 NCT03485911, APeX-S NCT03472040, APex-J NCT03873116) demonstrated the efficacy of Berotralstat as long-term prophylaxis for patients with HAE, which showed a reduction in the attack rate and on-demand medication usage. Berotralstat was well tolerated, and gastrointestinal treatment-emergent adverse events were generally mild and self-limited. Conclusion: Oral Berotralstat is an effective and safe long-term prophylactic treatment for patients with HAE that will provide patients unable to tolerate parenteral therapies with the option of disease control. Berotralstat may be associated with reduced treatment burden compared with injectable therapies, highlighting the importance of patient preference with regard to the administration route of their HAE prophylactic treatment.
A review of Berotralstat for the treatment of hereditary angioedema
Expert Rev Clin Immunol 2023 Feb;19(2):145-153.PMID:36408587DOI:10.1080/1744666X.2023.2150611.
Introduction: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) imposes a significant disease burden on patients and their families. Unpredictable episodes of angioedema, which can lead to life-threatening conditions, have a significant impact on the quality of life of the patient. The fundamental aim of the treatment of C1-INH-HAE is to ensure that patients can lead a normal life. The most effective way to do this is to prevent the onset of angioedema attacks. Areas covered: This review gives a brief overview of the safety and efficacy of the oral kallikrein inhibitor Berotralstat in C1-INH-HAE disease. It provides a comprehensive synopsis of the results of the first clinical trials with a targeted oral kallikrein inhibitor (APeX-1 [NCT02870972]; ZENITH-1 [NCT03240133]; APeX-2 [NCT03485911]; APeX-S [NCT03472040]; APeX-J [NCT03873116]), reviewing evidence on the efficacy and safety of the drug, and placing Berotralstat on the spectrum of long-term prophylactic therapeutic options. Expert opinion: The availability of the first targeted oral prophylactic drug, the kallikrein inhibitor Berotralstat, in 2021, is a milestone in the treatment of patients with hereditary angioedema.