Icatibant (acetate)
(Synonyms: 艾替班特乙酸盐,HOE 140 acetate) 目录号 : GC43888
A synthetic peptide antagonist of the bradykinin B2 receptor
Cas No.:138614-30-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Icatibant is a synthetic peptide antagonist of the bradykinin B2 receptor with IC50 and Ki values of 1.07 and 0.798 nM, respectively, in guinea pig ileal cell membranes. It inhibits bradykinin-induced contractions in isolated guinea pig ileum and pulmonary arteries as well as in rat uterus (IC50s = 11, 5.4, and 4.9 nM, respectively). In vivo, icatibant inhibits bronchoconstriction induced by bradykinin in a guinea pig model (ID50s = 13.4 and 31.8 pmol/kg, i.v., for pulmonary resistance and dynamic lung compliance, respectively). Icatibant (30 µg, i.v.) also reduces vascular permeability in the footpad and intestine in a mouse model of hereditary angioedema. Formulations containing icatibant have been used for the treatment of hereditary angioedema.
| Cas No. | 138614-30-9 | SDF | |
| 别名 | 艾替班特乙酸盐,HOE 140 acetate | ||
| Canonical SMILES | O=C(N1[C@](CCCC2)([H])[C@]2([H])C[C@H]1C(N[C@H](C(O)=O)CCCNC(N)=N)=O)[C@@H]3N(C([C@H](CO)NC([C@H](CC4=CC=CS4)NC(CNC([C@@H]5C[C@@H](O)CN5C([C@H]6N(C([C@@H](NC([C@H](N)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CCC6)=O)=O)=O)=O)=O)CC7=C(C=CC=C7)C3.OC(C)=O | ||
| 分子式 | C59H89N19O13S•XC2H4O2 | 分子量 | 1304.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 0.25 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | -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 | 0.7666 mL | 3.8329 mL | 7.6658 mL |
| 5 mM | 0.1533 mL | 0.7666 mL | 1.5332 mL |
| 10 mM | 0.0767 mL | 0.3833 mL | 0.7666 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。
Treatment of Hereditary Angioedema
J Investig Allergol Clin Immunol 2021 Feb;31(1):1-16.PMID:33602658DOI:10.18176/jiaci.0653.
Hereditary angioedema due to C1-esterase inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease. In the last decade, new drugs and new indications for old drugs have played a role in the management of C1-INH-HAE. This review examines current therapy for C1-INH-HAE and provides a brief summary of drugs that are under development. Increased knowledge of the pathophysiology of C1-INH-HAE has been crucial for advances in the field, with inhibition of the kallikrein-kinin system (plasma kallikrein, activated factor XII) as a key area in the discovery of new drugs, some of which are already marketed for treatment of C1-INH-HAE. Pharmacological treatment is based on 3 pillars: treatment of acute angioedema attacks (on-demand treatment), short-term (preprocedure) prophylaxis, and long-term prophylaxis. The 4 drugs that are currently available for the treatment of acute angioedema attacks (purified plasma-derived human C1 esterase inhibitor concentrate, Icatibant acetate, ecallantide, recombinant human C1 esterase inhibitor) are all authorized for self-administration, except ecallantide. Purified plasma-derived human C1 esterase inhibitor concentrate is the treatment of choice for short-term prophylaxis. Tranexamic acid, danazol, intravenous and subcutaneous nanofiltered purified plasma-derived human C1 esterase inhibitor concentrate, and lanadelumab can be used for long-term prophylaxis. New drugs are being investigated, mainly as long-term prophylaxis, and are aimed at blocking the kallikrein-kinin system by means of antiprekallikrein, antikallikrein, and anti-activated FXII action.
ACE inhibitor-mediated angioedema
Int Immunopharmacol 2020 Jan;78:106081.PMID:31835086DOI:10.1016/j.intimp.2019.106081.
Angioedema (AE) occurring during ACE inhibitor therapy (ACEi-AE) is a rare complication involving between 0.1 and 0.7% of treated patients. AE can also complicate other therapeutic regimens that block the renin-angiotensin aldosterone system. Other drugs, such as immune suppressors, some type of antidiabetics or calcium antagonists, can increase the likelihood of ACEi-AE when associated to ACEi. There is a clear ethnic predisposition, since African-Americans or Hispanics show a higher prevalence of this condition compared to Caucasians. At least in African-Americans the genetic predisposition accounts for a general higher prevalence of AE, independently from the cause. People that experience ACEi-AE may have some recurrence when they are switched to an angiotensin-receptor blocker (ARB); however, epidemiological studies on large cohorts have shown that angiotensin receptor blockers (ARB) do not increase the likelihood of AE compared to other antihypertensives. Clinical manifestations consist of edema of face, lips, tongue, uvula and upper airways, requiring intubation or tracheotomy in severe cases. Attacks last for 48-72 h and require hospital admission in most cases. Intestinal involvement with sub-occlusive symptoms has also been reported. The pathogenesis of ACEi-AE depends mainly on a reduced catabolism and accumulation of bradykinin, which is normally metabolized by ACE. Genetic studies have shown that some single nucleotide polymorphisms at genes encoding relevant molecules for bradykinin metabolism and action may be involved in ACEi-AE, giving a basis for the ethnic predisposition. Treatment of ACEi-AE is still a matter of debate. Corticosteroids and antihistamines do not show efficacy. Some therapeutic attempts have shown some efficacy for fresh frozen plasma or C1 inhibitor concentrate infusion. Interventional studies with the specific bradykinin receptor antagonist Icatibant have shown conflicting results; there might be a different ethnic predisposition to Icatibant efficacy which has been proven in caucasian but not in black patients.
Icatibant
Drugs 2010;70(1):73-81.PMID:20030426DOI:10.2165/11204500-000000000-00000.
Icatibant is a selective antagonist of the bradykinin type 2 receptor. In the randomized, double-blind, multicentre, FAST-1 trial, the difference in the median time to the onset of symptom relief (primary endpoint) did not reach statistical significance between a single dose of subcutaneous Icatibant 30 mg and placebo in adults with moderate to very severe acute abdominal or cutaneous episodes of hereditary angioedema. However, Icatibant was effective with regard to several other endpoints, providing significantly greater reductions from baseline in symptom severity scores 4 and 12 hours after administration, and eliciting significantly shorter times to both first symptom improvement and overall patient improvement than placebo. In the similarly designed, active comparator-controlled, FAST-2 trial, a single dose of subcutaneous Icatibant 30 mg was associated with a significantly shorter median time to onset of symptom relief (primary endpoint) than oral tranexamic acid in adults with acute abdominal or cutaneous episodes of hereditary angioedema, and was also more effective than tranexamic acid in terms of most other endpoints. Across both FAST-1 and -2, the efficacy of subcutaneous Icatibant 30 mg in the treatment of laryngeal episodes of hereditary angioedema was generally consistent with that seen for abdominal and cutaneous episodes, with a median time to first symptom improvement of 0.6-1.0 hours. Subcutaneous Icatibant was generally well tolerated in adult patients with hereditary angioedema in the FAST trials, with the most common adverse events being injection-site reactions that were generally of mild severity, transient in nature and resolved spontaneously without treatment.
Hereditary angioedema: an update on causes, manifestations and treatment
Br J Hosp Med (Lond) 2019 Jul 2;80(7):391-398.PMID:31283393DOI:10.12968/hmed.2019.80.7.391.
Hereditary angioedema is a rare genetic disorder caused by deficiency of C1 esterase inhibitor (C1-INH) and characterized by recurrent episodes of severe swelling that affect the limbs, face, intestinal tract and airway. Since laryngeal oedema can be life-threatening as a result of asphyxiation, correct diagnosis and management of hereditary angioedema is vital. Hereditary angioedema attacks are mediated by bradykinin, the production of which is regulated by C1-INH. Hereditary angioedema therapy relies on treatment of acute attacks, and short- and long-term prophylaxis. Acute treatment options include C1-INH concentrate, Icatibant and ecallantide. Self-administration of treatment is recommended and is associated with increased quality of life of patients with hereditary angioedema. Advances in diagnosis and management have improved the outcomes and quality of life of patients with hereditary angioedema.
Is Icatibant Safe for the Treatment of Hereditary Angioedema During Pregnancy?
Curr Allergy Asthma Rep 2022 Oct;22(10):135-140.PMID:36044174DOI:10.1007/s11882-022-01040-3.
Purpose of review: Hereditary angioedema (HAE) is a disorder affecting bradykinin regulation presenting as recurrent cutaneous or mucosal swelling. Treatment options include plasma-derived or human-recombinant C1-inhibitor, Icatibant, or ecallantide. Due to the lack of knowledge and experience on the topic, the treatment of choice in pregnancy is plasma-derived C1-inhibitor, and reporting any new experience is recommended. This review presents current guidelines for HAE treatment with a focus on pregnancy and reviews all experience with Icatibant use during pregnancy. Recent findings: Our experience of treating a pregnant nC1-INH HAE patient with Icatibant is presented, with no adverse effects or abnormalities, to add to the growing knowledge of Icatibant use during pregnancy. Considering the limited number of attacks that our patient usually experiences, which continued at more or less the same frequency during pregnancy, we feel Icatibant to be a safe choice for on-demand HAE treatment during pregnancy for such cases.