Atogepant
(Synonyms: MK-8031; AGN-241689) 目录号 : GC65596
Atogepant (MK-8031) 是一种口服有效且具有选择性的降钙素基因相关肽受体 (CGRP) 拮抗剂。Atogepant 可用于研究偏头痛。
Cas No.:1374248-81-3
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
Atogepant (MK-8031) is an orally active and selective calcitonin gene-related peptide receptor (CGRP) antagonist. Atogepant can be used for researching migraine[1].
[1]. Ailani J, et al. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021 Aug 19;385(8):695-706.
| Cas No. | 1374248-81-3 | SDF | Download SDF |
| 别名 | MK-8031; AGN-241689 | ||
| 分子式 | C29H23F6N5O3 | 分子量 | 603.52 |
| 溶解度 | DMSO : 100 mg/mL (165.69 mM; Need ultrasonic) | 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 | 1.6569 mL | 8.2847 mL | 16.5695 mL |
| 5 mM | 0.3314 mL | 1.6569 mL | 3.3139 mL |
| 10 mM | 0.1657 mL | 0.8285 mL | 1.6569 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。
Atogepant for the Preventive Treatment of Migraine
N Engl J Med 2021 Aug 19;385(8):695-706.PMID:34407343DOI:10.1056/NEJMoa2035908.
Background: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist that is being investigated for the preventive treatment of migraine. Methods: In a phase 3, double-blind trial, we randomly assigned adults with 4 to 14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of oral Atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks. The primary end point was the change from baseline in the mean number of migraine days per month across the 12 weeks. Secondary end points included headache days per month, a reduction from baseline of at least 50% in the 3-month average of migraine days per month, quality of life, and scores on the Activity Impairment in Migraine-Diary (AIM-D). Results: A total of 2270 participants were screened, 910 were enrolled, and 873 were included in the efficacy analysis; 214 were assigned to the 10-mg Atogepant group, 223 to the 30-mg Atogepant group, 222 to the 60-mg Atogepant group, and 214 to the placebo group. The mean number of migraine days per month at baseline ranged from 7.5 to 7.9 in the four groups. The changes from baseline across 12 weeks were -3.7 days with 10-mg Atogepant, -3.9 days with 30-mg Atogepant, -4.2 days with 60-mg Atogepant, and -2.5 days with placebo. The mean differences from placebo in the change from baseline were -1.2 days with 10-mg Atogepant (95% confidence interval [CI], -1.8 to -0.6), -1.4 days with 30-mg Atogepant (95% CI, -1.9 to -0.8), and -1.7 days with 60-mg Atogepant (95% CI, -2.3 to -1.2) (P<0.001 for all comparisons with placebo). Results for the secondary end points favored Atogepant over placebo with the exceptions of the AIM-D Performance of Daily Activities score and the AIM-D Physical Impairment score for the 10-mg dose. The most common adverse events were constipation (6.9 to 7.7% across Atogepant doses) and nausea (4.4 to 6.1% across Atogepant doses). Serious adverse events included one case each of asthma and optic neuritis in the 10-mg Atogepant group. Conclusions: Oral Atogepant once daily was effective in reducing the number of migraine days and headache days over a period of 12 weeks. Adverse events included constipation and nausea. Longer and larger trials are needed to determine the effect and safety of Atogepant for migraine prevention. (Funded by Allergan; ADVANCE ClinicalTrials.gov number, NCT03777059.).
Atogepant: First Approval
Drugs 2022 Jan;82(1):65-70.PMID:34813050DOI:10.1007/s40265-021-01644-5.
Atogepant (Qulipta™) is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by AbbVie for the prophylaxis of migraine. In September 2021, Atogepant was approved in the USA for the preventive treatment of episodic migraine in adults. The drug is also in phase 3 clinical development for the preventive treatment of migraine in various other countries. This article summarizes the milestones in the development of Atogepant leading to this first approval for the preventive treatment of episodic migraine in adults.
Atogepant for the prevention of episodic migraine in adults
SAGE Open Med 2022 Oct 6;10:20503121221128688.PMID:36226229DOI:10.1177/20503121221128688.
Objective: Atogepant is a newly approved medication for the prevention of migraine. This review aims to discuss the efficacy, safety, cost, and place in therapy of Atogepant. Methods: The authors performed a systematic search for sources, including articles, abstracts, and poster presentations. Queried databases were the National Institute of Health, US National Library of Medicine Clinical Trials, PubMed, European PMC, and the Cochrane Library. Search terms included Atogepant, QULIPTA™, AGN-241689, MK-803, and N02CD07. Full-text, English language, randomized-controlled trials from 1 February 2012 to 1 February 2022 were included in the review. Additional relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review. A total of 193 database entries were evaluated for inclusion in this narrative review. Three articles representing two randomized controlled trials were reviewed. Results and conclusions: Atogepant, a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is a daily oral treatment for migraine prevention. In placebo-controlled clinical trials, Atogepant decreased mean monthly migraine days (MMD) over 12 weeks in patients with episodic migraine. Major treatment-related adverse effects include nausea and constipation. Long-term placebo-controlled efficacy and safety studies, chronic migraine studies, and studies in patients that failed more than two classes of preventive therapies are still pending. Atogepant represents one of many novel therapies for the prevention of migraine. To date, no head-to-head comparisons of Atogepant versus other agents indicated for migraine prevention have been published. Atogepant offers patients an alternative therapy to injectable or infusion monoclonal antibody treatments and offers an alternative to non-specific migraine medications that are associated with poor tolerability. Due to its high cost and narrower therapeutic indications, Atogepant may be reserved for a small subset of migraineurs who prefer oral therapy.
Time course of efficacy of Atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial
Cephalalgia 2022 Jan;42(1):3-11.PMID:34521260DOI:10.1177/03331024211042385.
Background: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of migraine. Methods: In the double-blind, phase 3 ADVANCE trial, participants with 4-14 migraine days/month were randomized to Atogepant 10 mg, 30 mg, 60 mg, or placebo once daily for 12 weeks. We evaluated the time course of efficacy of Atogepant for the preventive treatment of migraine. Analyses included change from baseline in mean monthly migraine days during each of the three 4-week treatment periods, change in weekly migraine days during weeks 1-4, and proportion of participants with a migraine on each day during the first week. Results: We analyzed 873 participants (n = 214 Atogepant 10 mg, n = 223 Atogepant 30 mg, n = 222 Atogepant 60 mg, n = 214 placebo). For weeks 1-4, mean change from baseline in mean monthly migraine days ranged from -3.1 to -3.9 across Atogepant doses vs -1.6 for placebo (p < 0.0001). For weeks 5-8 and 9-12, reductions in mean monthly migraine days ranged from -3.7 to -4.2 for Atogepant vs -2.9 for placebo (p ≤ 0.012) and -4.2 to -4.4 for Atogepant vs -3.0 for placebo (p < 0.0002), respectively. Mean change from baseline in weekly migraine days in week 1 ranged from -0.77 to -1.03 for Atogepant vs -0.29 with placebo (p < 0.0001). Percentages of participants reporting a migraine on post-dose day 1 ranged from 10.8% to 14.1% for Atogepant vs 25.2% with placebo (p ≤ 0.0071). Conclusion: Atogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period.Clinical trial registration: ClinicalTrials.gov identifier: NCT03777059.
Atogepant: an emerging treatment for migraine
Expert Opin Pharmacother 2022 Apr;23(6):653-662.PMID:35319319DOI:10.1080/14656566.2022.2057221.
Introduction: Until recently, only nonspecific and not always well-tolerated medications were available for migraine prophylaxis. Currently, specific drugs such as calcitonin gene-related peptide (CGRP) monoclonal antibodies and second-generation gepants are marketed for migraine treatment. Atogepant, an orally active small molecule, is a potent, selective antagonist of the CGRP receptor and is the only gepant authorized exclusively for episodic migraine prophylaxis in adults. Areas covered: Using literature obtained from PubMed, Scopus, Web of Science, Cochrane, and ClinicalTrials.gov (up to February 13rd, 2022), the authors summarize and evaluate the available data on Atogepant for the prophylaxis of episodic migraine. Expert opinion: From pivotal trials, the efficacy and tolerability of Atogepant in episodic migraine prophylaxis seem comparable to those of CGRP monoclonal antibodies, even if comparative studies have not been conducted. To date, limited information is available on Atogepant, including the optimal dose and duration of therapy; hence, it is difficult to establish whether it could be a first-line drug for migraine prophylaxis. Furthermore, it is important to evaluate if Atogepant use is associated with the risk of cardiovascular and cerebrovascular events, which could result from potent and persistent blockade of vasodilation by CGRP.