Anakinra
(Synonyms: 阿那白滞素; AMG-719) 目录号 : GC39339阿那白滞素(Anakinra)是一种重组的、非糖基化的人类白细胞介素-1受体拮抗剂（IL-1Ra）。
Cas No.:143090-92-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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Purity:≥95.00%
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| Animal experiment [1]: | |
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Animal models |
Immunodeficient mice |
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Preparation Method |
The simultaneous administration of Etanercept (at a dosage of 5 mg/kg, via intraperitoneal injection) coupled with daily Anakinra (at a dosage of 100 mg/kg, also via intraperitoneal injection for a period of 7 days). |
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Dosage form |
100 mg/kg, daily for 7 days, intraperitoneal injection |
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Applications |
The simultaneous administration of Etanercept coupled with daily Anakinra significantly enhanced the engraftment of marginal mass human islets in immunodeficient mice. |
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References: |
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Anakinra (AMG-719, Raleukin) is a recombinant, non glycosylated human interleukin-1 receptor antagonist (IL-1Ra). It is produced using DNA recombination technology in the Escherichia coli expression system andamino acid sequence is MRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQGPNVNLEEKIDVVPIEPHALFLGIHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQDKRFAFIRSDSGPTTSFESAACPGWFLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE. Anakinra represents the inaugural biological therapy designed to neutralize the inflammatory actions of IL-1[1][2]. Anakinra has been proven effective for the treatment of various inflammatory and autoimmune diseases, including Still's disease[3].
Anakinra was administered at a dose of 100 mg/kg via intraperitoneal injection, and the same route was used to administer Etanercept at a dose of 5 mg/kg daily for seven consecutive days, which significantly facilitated the successful implantation of marginal quality human islet cells in mice with impaired immune systems [2]. Anakinra enhances tumor growth inhibition in mice receiving peptide vaccination and treated with beta-(1-3),(1-6)-D-glucan by blocking the IL-1 receptor and reducing IL-1-induced IL-6 production[4].
References:
[1] Cvetkovic RS, et al. Anakinra. BioDrugs. 2002;16(4):303-11; discussion 313-4.
[2] McCall M, et al. Anakinra potentiates the protective effects of etanercept in transplantation of marginal mass human islets in immunodeficient mice. Am J Transplant. 2012 Feb;12(2):322-9.
[3] Vastert Sebastiaan J, et al. Anakinra in children and adults with Still's disease. Rheumatology (Oxford) 2019 Nov 1;58(Suppl 6):vi9-vi22. PMID:31769856. DOI:10.1093/rheumatology/kez350.
[4] Harnack U, et al. IL-1 receptor antagonist anakinra enhances tumour growth inhibition in mice receiving peptide vaccination and beta-(1-3),(1-6)-D-glucan. Anticancer Res. 2010 Oct;30(10):3959-65.
阿那白滞素(Anakinra)是一种重组的、非糖基化的人类白细胞介素-1受体拮抗剂（IL-1Ra）。它是利用大肠杆菌表达系统的DNA重组技术生产的，并且氨基酸序列为MRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQGPNVNLEEKIDVVPIEPHALFLGIHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQDKRFAFIRSDSGPTTSFESAACPGWFLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE。阿那白滞素代表了首个旨在中和IL-1炎症作用的生物疗法[1][2]。阿那白滞素已被证明可用于治疗斯蒂尔病等多种炎症和自身免疫性疾病[3]。
阿那白滞素通过腹腔注射100 mg/kg，以及相同途径每日给予依那西普（Etanercept）5 mg/kg的剂量，连续7天，显著促进了在免疫系统受损的小鼠中，边缘质量的人类胰岛细胞的成功植入[2]。阿那白滞素通过阻断 IL-1 受体来减少 IL-1 诱导的 IL-6 生成，增强了接受肽疫苗接种并经β-(1-3),(1-6)-D-葡聚糖处理的小鼠中肿瘤生长的抑制[4]。
| Cas No. | 143090-92-0 | SDF | |
| 别名 | 阿那白滞素; AMG-719 | ||
| Canonical SMILES | [Anakinra] | ||
| 分子式 | C759H1186N208O232S10 | 分子量 | 17257.6 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at 4°C, do not freeze |
| 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 | 0.0579 mL | 0.2897 mL | 0.5795 mL |
| 5 mM | 0.0116 mL | 0.0579 mL | 0.1159 mL |
| 10 mM | 0.0058 mL | 0.029 mL | 0.0579 mL |
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| 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 | ||||||||||
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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。
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Anakinra in children and adults with Still's disease
Rheumatology (Oxford) 2019 Nov 1;58(Suppl 6):vi9-vi22.PMID:31769856DOI:10.1093/rheumatology/kez350.
Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these being one disease-Still's disease-with different ages of onset. Anakinra was recently approved by the European Medicines Agency for Still's disease. In this review we discuss the reasoning for considering Still's disease as one disease and present Anakinra efficacy and safety based on the available literature. The analysis of 27 studies showed that response to Anakinra in Still's disease was remarkable, with clinically inactive disease or the equivalent reported for 23-100% of patients. Glucocorticoid reduction and/or stoppage was reported universally across the studies. In studies on paediatric patients where Anakinra was used early or as first-line treatment, clinically inactive disease and successful Anakinra tapering/stopping occurred in >50% of patients. Overall, current data support targeted therapy with Anakinra in Still's disease since it improves clinical outcome, especially if initiated early in the disease course.
The use of Anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis
Pediatr Blood Cancer 2020 Nov;67(11):e28581.PMID:32725881DOI:10.1002/pbc.28581.
Background: Hemophagocytic lymphohistiocytosis (HLH) can be familial or secondary, which is often triggered by infection or malignancy. HLH therapy includes dexamethasone and etoposide. However, therapy is associated with significant morbidity and mortality. Anakinra, a recombinant interleukin-1 receptor antagonist, has been reported to treat macrophage activation syndrome (MAS), rheumatic sHLH. We report our experience with Anakinra to treat patients with nonrheumatic secondary HLH (sHLH). Procedure: Six children were diagnosed with HLH from December 2014 to August 2016 and were treated with subcutaneous Anakinra (6-10 mg/kg/day divided over four doses) with or without dexamethasone (10 mg/m2 /day). Therapy was either escalated or weaned based on clinical and laboratory response. Results: Five of six patients were treated with Anakinra and dexamethasone, and one with Anakinra alone due to active cytomegalovirus (CMV) pneumonitis. The median age of diagnosis was 1.8 years (range 0.8-14.9 years). No pathogenic mutations associated with HLH were identified, but three of six possessed genetic variants of unknown significance. Infectious triggers were identified for four patients and two patients had malignancies. The average treatment duration was 8 weeks with 3.5-5.5 years of follow up. No patient needed escalation of therapy to include etoposide. All patients achieved remission. Anakinra was well tolerated without significant adverse effects. Conclusion: Initial treatment with Anakinra (with or without dexamethasone) is a feasible treatment alternative for patients with secondary HLH and may allow for avoidance of etoposide. We recommend early initiation of Anakinra when HLH is suspected. A broader investigation of the use of Anakinra as a first-line agent for HLH is ongoing.
Single-center experience using Anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
J Immunother Cancer 2022 Jan;10(1):e003847.PMID:34996813DOI:10.1136/jitc-2021-003847.
In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, Anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, Anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with Anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after Anakinra treatment. With three daily subcutaneous doses, Anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of Anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to Anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings.
Efficacy and secondary infection risk of tocilizumab, sarilumab and Anakinra in COVID-19 patients: A systematic review and meta-analysis
Rev Med Virol 2022 May;32(3):e2295.PMID:34558756DOI:10.1002/rmv.2295.
As the pandemic progresses, the pathophysiology of coronavirus disease 2019 (COVID-19) is becoming clearer and the potential for immunotherapy is increasing. However, clinical efficacy and safety of immunosuppressants (including tocilizumab, sarilumab and Anakinra) treatment in COVID-19 patients are not yet known. We searched PubMed, Embase Medline, Web of Science and MedRxiv using specific search terms in studies published from 1 January 2020 to 20 December 2020. In total, 33 studies, including 3073 cases and 6502 controls, were selected for meta-analysis. We found that immunosuppressant therapy significantly decreased mortality in COVID-19 patients on overall analysis (odds ratio = 0.71, 95% confidence interval = 0.57-0.89, p = 0.004). We also found that tocilizumab and Anakinra significantly decreased mortality in patients without any increased risk of secondary infection. In addition, we found similar results in several subgroups. However, we found that tocilizumab therapy significantly increased the risk of fungal co-infections in COVID-19 patients. This represents the only systematic review and meta-analysis to investigate the efficacy and secondary infection risk of immunosuppressant treatment in COVID-19 patients. Overall, immunosuppressants significantly decreased mortality but had no effect on increased risk of secondary infections. Our analysis of tocilizumab therapy showed a significantly increased risk of fungal co-infections in these patients.
Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy
J Clin Invest 2022 Jan 18;132(2):e144983.PMID:34847078DOI:10.1172/JCI144983.
Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here, we define a molecular pathway through which recombinant IL-1 receptor antagonist (IL-1Ra, Anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynurenine pathway, transcriptionally activated NADPH oxidase 4 independent of the IL-1R1. By coupling the mitochondrial redox balance to autophagy, Anakinra improved the dysregulated proteostasis network in murine and human cystic fibrosis. We anticipate that Anakinra may represent a therapeutic option in addition to its IL-1R1-dependent antiinflammatory properties by acting at the intersection of mitochondrial oxidative stress and autophagy with the capacity to restore conditions in which defective proteostasis leads to human disease.