AMY-101
(Synonyms: Cp40) 目录号 : GC39697
AMY-101 (Cp40) 是补体 C3 的肽类抑制剂 (KD = 0.5 nM)，可抑制非人类灵长类动物自然发生的牙周炎。AMY-101 (Cp40) 在 COVID-19 重症肺炎合并全身超炎症模型中具有良好的抗炎活性。
Cas No.:1427001-89-5
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
AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3 (KD = 0.5 nM), inhibits naturally occurring periodontitis in non-human primates (NHPs). AMY-101 (Cp40) exhibits a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation[1][2].
[1]. Kajikawa T, et al. Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates. Mol Ther Methods Clin Dev. 2017 Aug 18;6:207-215. [2]. Mastaglio S, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020 Apr 29:108450
| Cas No. | 1427001-89-5 | SDF | |
| 别名 | Cp40 | ||
| 分子式 | C83H117N23O18S2 | 分子量 | 1789.11 |
| 溶解度 | 100mg/mL in Water | 储存条件 | Store at -20°C, Protect from light |
| 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 | 0.5589 mL | 2.7947 mL | 5.5894 mL |
| 5 mM | 0.1118 mL | 0.5589 mL | 1.1179 mL |
| 10 mM | 0.0559 mL | 0.2795 mL | 0.5589 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。
Complement C3 inhibition in severe COVID-19 using compstatin AMY-101
Sci Adv 2022 Aug 19;8(33):eabo2341.PMID:35977025DOI:10.1126/sciadv.abo2341.
Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.
Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy
Pharmaceuticals (Basel) 2022 Jul 9;15(7):845.PMID:35890144DOI:10.3390/ph15070845.
Thrombotic microangiopathy (TMA) is a complication that may occur after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and is conventionally called transplant-associated thrombotic microangiopathy (TA-TMA). Despite the many efforts made to understand the mechanisms of TA-TMA, its pathogenesis is largely unknown, its diagnosis is challenging and the case-fatality rate remains high. The hallmarks of TA-TMA, as for any TMA, are platelet consumption, hemolysis, and organ dysfunction, particularly the kidney, leading also to hypertension. However, coexisting complications, such as infections and/or immune-mediated injury and/or drug toxicity, together with the heterogeneity of diagnostic criteria, render the diagnosis difficult. During the last 10 years, evidence has been provided on the involvement of the complement system in the pathophysiology of TA-TMA, supported by functional, genetic, and therapeutic data. Complement dysregulation is believed to collaborate with other proinflammatory and procoagulant factors to cause endothelial injury and consequent microvascular thrombosis and tissue damage. However, data on complement activation in TA-TMA are not sufficient to support a systematic use of complement inhibition therapy in all patients. Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101).
Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation
J Clin Invest 2021 Dec 1;131(23):e152973.PMID:34618684DOI:10.1172/JCI152973.
BackgroundGingivitis and periodontitis are prevalent inflammatory diseases of the periodontal tissues. Current treatments are often ineffective or do not prevent disease recurrence. Uncontrolled complement activation and the resulting chronic gingival inflammation are hallmarks of periodontal diseases. We determined the efficacy and safety of a complement 3-targeted therapeutic, AMY-101, which was locally administered to adult patients with periodontal inflammation.MethodsThirty-two patients with gingival inflammation were enrolled in a randomized, placebo-controlled, double-blind, split-mouth phase IIa trial that followed a dose escalation study to select a safe and effective dose in an additional 8 patients. Half of the patient's mouth was randomly assigned to AMY-101 (0.1 mg/site) or placebo injections at sites of inflammation, administered on days 0, 7, and 14, and then evaluated for safety and efficacy outcomes on days 28, 60, and 90. The primary efficacy outcome was a change in gingival inflammation, measured by a modified gingival index (MGI), and secondary outcomes included changes in bleeding on probing (BOP), the amount of plaque, pocket depth, clinical attachment level, and gingival crevicular fluid levels of matrix metalloproteinases (MMPs) over 90 days.ResultsA once-weekly intragingival injection of AMY-101 for 3 weeks was safe and well tolerated in all participants and resulted in significant (P < 0.001) reductions in clinical indices measuring gingival inflammation (MGI and BOP). AMY-101 significantly (P < 0.05) reduced MMP-8 and MMP-9 levels, indicators of inflammatory tissue destruction. These therapeutic effects persisted for at least 3 months after treatment.ConclusionAMY-101 treatment resulted in a significant and sustainable reduction in gingival inflammation without adverse events and, we believe, merits further investigation for the treatment of periodontitis and other oral or peri-implant inflammatory conditions.Trial registrationClinicalTrials.gov identifier NCT03694444.FundingAmyndas Pharmaceuticals.
How the Innate Immune System of the Blood Contributes to Systemic Pathology in COVID-19-Induced ARDS and Provides Potential Targets for Treatment
Front Immunol 2022 Mar 8;13:840137.PMID:35350780DOI:10.3389/fimmu.2022.840137.
Most SARS-CoV-2 infected patients experience influenza-like symptoms of low or moderate severity. But, already in 2020 early during the pandemic it became obvious that many patients had a high incidence of thrombotic complications, which prompted treatment with high doses of low-molecular-weight heparin (LMWH; typically 150-300IU/kg) to prevent thrombosis. In some patients, the disease aggravated after approximately 10 days and turned into a full-blown acute respiratory distress syndrome (ARDS)-like pulmonary inflammation with endothelialitis, thrombosis and vascular angiogenesis, which often lead to intensive care treatment with ventilator support. This stage of the disease is characterized by dysregulation of cytokines and chemokines, in particular with high IL-6 levels, and also by reduced oxygen saturation, high risk of thrombosis, and signs of severe pulmonary damage with ground glass opacities. The direct link between SARS-CoV-2 and the COVID-19-associated lung injury is not clear. Indirect evidence speaks in favor of a thromboinflammatory reaction, which may be initiated by the virus itself and by infected damaged and/or apoptotic cells. We and others have demonstrated that life-threatening COVID-19 ARDS is associated with a strong activation of the intravascular innate immune system (IIIS). In support of this notion is that activation of the complement and kallikrein/kinin (KK) systems predict survival, the necessity for usage of mechanical ventilation, acute kidney injury and, in the case of MBL, also coagulation system activation with thromboembolism. The general properties of the IIIS can easily be translated into mechanisms of COVID-19 pathophysiology. The prognostic value of complement and KKsystem biomarkers demonstrate that pharmaceuticals, which are licensed or have passed the phase I trial stage are promising candidate drugs for treatment of COVID-19. Examples of such compounds include complement inhibitors AMY-101 and eculizumab (targeting C3 and C5, respectively) as well as kallikrein inhibitors ecallantide and lanadelumab and the bradykinin receptor (BKR) 2 antagonist icatibant. In this conceptual review we discuss the activation, crosstalk and the therapeutic options that are available for regulation of the IIIS.
Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates
Mol Ther Methods Clin Dev 2017 Aug 18;6:207-215.PMID:28879212DOI:10.1016/j.omtm.2017.08.001.
Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs) when given once a week. This study was undertaken to determine the local safety of increasing doses of the drug as well as its efficacy when given at a reduced frequency or after systemic administration. Our findings have determined a local dose of AMY-101 (0.1 mg/site) that is free of local irritation and effective when given once every 3 weeks. Moreover, a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight) was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria) can additionally benefit in terms of improved periodontal condition. In summary, AMY-101 appears to be a promising candidate drug for the adjunctive treatment of human periodontitis, a notion that merits investigation in human clinical trials.