H-Glu-Ala-Met-His-Ser-Phe-Cys(1)-Ala-Phe-Lys-Ala-Asp-Asp-Gly-Pro-Cys(2)-Arg-Ala-Ala-His-Pro-Arg-Trp-Phe-Phe-Asn-Ile-Phe-aThr-Arg-Gln-Cys(3)-Glu-Glu-Phe-Ile-Tyr-Gly-Gly-Cys(2)-Glu-Gly-Asn-Gln-Asn-Arg-Phe-Glu-Ser-Leu-Glu-Glu-Cys(3)-Lys-Lys-Met-Cys(1)-aThr-Arg-Asp-OH

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: H-Glu-Ala-Met-His-Ser-Phe-Cys(1)-Ala-Phe-Lys-Ala-Asp-Asp-Gly-Pro-Cys(2)-Arg-Ala-Ala-His-Pro-Arg-Trp-Phe-Phe-Asn-Ile-Phe-aThr-Arg-Gln-Cys(3)-Glu-Glu-Phe-Ile-Tyr-Gly-Gly-Cys(2)-Glu-Gly-Asn-Gln-Asn-Arg-Phe-Glu-Ser-Leu-Glu-Glu-Cys(3)-Lys-Lys-Met-Cys(1)-aThr-Arg-Asp-OH
• 英文别名: (2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(1R,2aS,4S,5aS,8aS,11aR,13S,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,84S,87R,96S,99S)-22,42,45-tris(4-aminobutyl)-31-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-29a,72,78-tris(2-amino-2-oxoethyl)-14a,75-bis(3-amino-3-oxopropyl)-2a,23a,25,32a,35a,66-hexabenzyl-26a,99-bis[(2S)-butan-2-yl]-17a,41a,59a,69-tetrakis(3-carbamimidamidopropyl)-5a,8a,51,54,63,84-hexakis(2-carboxyethyl)-13,16-bis(carboxymethyl)-20a-[(1S)-1-hydroxyethyl]-60-(hydroxymethyl)-96-[(4-hydroxyphenyl)methyl]-50a-(1H-imidazol-5-ylmethyl)-38a-(1H-indol-3-ylmethyl)-19,28,53a,56a-tetramethyl-57-(2-methylpropyl)-39-(2-methylsulfanylethyl)-1a,3,4a,7a,9,10a,12,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,6a,8,9a,11,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.04,8.0144,148]nonahexacontahectane-36-carbonyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]butanedioic acid
• 化学式: C₃₀₅H₄₄₂N₈₈O₉₁S₈
• 分子量: 7054.0
• InChiKey: VBGWSQKGUZHFPS-VGMMZINCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -27.9
• 重原子数：
  492
• 可旋转键数：
  133
• 环数：
  17.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  3120
• 氢给体数：
  100
• 氢受体数：
  110

ADMET

毒理性

• 药物性肝损伤

化合物：艾卡拉肽

Compound:ecallantide

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今日，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按在人类中发展药物诱导肝损伤风险排名的最大参考药物清单。药物发现今日2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 毒性总结

识别和使用：Ecallantide，一种基于人类组织因子途径抑制剂第一个Kunitz结构域的生物合成蛋白，是一种可逆的、选择性的血浆激肽释放酶抑制剂。Ecallantide是一种无色透明的溶液。Ecallantide用于治疗12岁及以上患者的遗传性血管性水肿（HAE）的急性发作。人类暴露和毒性：目前尚未有关于Ecallantide过量的报告。HAE患者在单次静脉注射高达90毫克的剂量下，没有出现剂量相关的毒性证据。在接受Ecallantide治疗的病人中，已经发生了潜在的严重超敏反应，包括过敏性休克。在临床研究中，255名接受静脉或皮下注射Ecallantide的遗传性血管性水肿（HAE）患者中，有10名患者（4%）经历了过敏性休克。在187名接受皮下注射Ecallantide的患者亚组中，有5名患者（3%）经历了过敏性休克。与这些反应相关的症状包括胸痛、潮红、咽部水肿、瘙痒、流涕、打喷嚏、鼻塞、喉咙刺激、荨麻疹、喘息和低血压。这些反应在给药后第一个小时内发生。其他表明超敏反应的不良反应包括以下几种：瘙痒（5%）、皮疹（3%）和荨麻疹（2%）。动物研究：在大鼠中进行了为期两年的研究，以评估Ecallantide的致癌潜力。在大鼠中，没有观察到在每三天一次皮下注射剂量高达10 mg/kg（大约是最大推荐人类剂量（MRHD）的两倍，基于AUC）的肿瘤生成。在大鼠中，静脉注射的Ecallantide剂量大约是最大推荐人类剂量（MRHD）的13倍（以mg/kg计，在大鼠母体剂量为15 mg/kg/天的剂量下），在轻度母体毒性存在的情况下，导致早期吸收和每胎吸收的胚胎比例增加。在大鼠中，接受大约是MRHD 8倍的静脉注射剂量（在大鼠母体剂量为10 mg/kg/天的情况下），没有观察到发育毒性。在大鼠中，皮下注射剂量高达大约是MRHD 2.4倍的Ecallantide（在大鼠母体剂量为20 mg/kg/天的情况下），以及在接受静脉注射剂量高达大约是MRHD 6倍的兔中（在兔母体剂量为5 mg/kg/天的情况下），对胚胎胎儿发育没有不良影响。在大鼠中，皮下注射剂量高达25 mg/kg/天的Ecallantide对生育能力和生殖性能没有影响（大约是MRHD的21倍）。

IDENTIFICATION AND USE: Ecallantide, a biosynthetic protein based on the first Kunitz domain of human tissue factor pathway inhibitor, is a reversible and selective inhibitor of plasma kallikrein. Ecallantide is a clear, colorless solution. Ecallantide is indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older. HUMAN EXPOSURE AND TOXICITY: There have been no reports of overdose with ecallantide. HAE patients have received single doses up to 90 mg intravenously without evidence of dose-related toxicity. Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with ecallantide. In 255 hereditary angioedema (HAE) patients treated with intravenous or subcutaneous ecallantide in clinical studies, 10 patients (4%) experienced anaphylaxis. For the subgroup of 187 patients treated with subcutaneous ecallantide, 5 patients (3%) experienced anaphylaxis. Symptoms associated with these reactions have included chest discomfort, flushing, pharyngeal edema, pruritus, rhinorrhea, sneezing, nasal congestion, throat irritation, urticaria, wheezing, and hypotension. These reactions occurred within the first hour after dosing. Other adverse reactions indicative of hypersensitivity reactions included the following: pruritus (5%), rash (3%), and urticaria (2%). ANIMAL STUDIES: A two-year study was conducted in rats to assess the carcinogenic potential of ecallantide. No evidence of tumorigenicity was observed in rats at doses up to 10 mg/kg administered subcutaneously every three days (approximately 2-fold greater than the maximum recommended human dose (MRHD) on an AUC basis). In rats, intravenous ecallantide at a dose approximately 13 times the maximum recommended human dose (MRHD) (on a mg/kg basis at a maternal dose of 15 mg/kg/day in rats) caused increased numbers of early resorptions and percentages of resorbed conceptuses per litter in the presence of mild maternal toxicity. No development toxicity was observed in rats that received an intravenous dose approximately 8 times the MRHD (at a maternal dose of 10 mg/kg/day in rats). There were no adverse effects of ecallantide on embryofetal development in rats that received subcutaneous doses up to approximately 2.4 times the MRHD (at a maternal dose of 20 mg/kg/day in rats), and in rabbits that received intravenous doses up to approximately 6 times the MRHD (at a maternal dose of 5 mg/kg/day in rabbits). Ecallantide had no effects on fertility and reproductive performance in rats at subcutaneous doses up to 25 mg/kg/day (approximately 21 times MRDH).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项健康个体的药代动力学研究中，ecallantide的峰值血浆浓度在大约30毫克ecallantide通过皮下注射给药后2-3小时达到；报告显示，皮下给药的生物利用度大约为90%。

In a pharmacokinetic study in healthy individuals, peak plasma concentrations of ecallantide were achieved at approximately 2-3 hours following a 30 mg dose of ecallantide administered by subcutaneous injection; an approximate bioavailability of 90% was reported with subcutaneous administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Ecallantide是一种小分子蛋白质，通过尿液排出；然而，由于这种药物是一种小分子蛋白质，因此代谢分解（或降解）也是一种可能的消除过程。

Ecallantide is eliminated in urine; however, since the drug is a small protein, metabolic catabolism (or degradation) is also a likely elimination process.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚ecallantide是否经人乳排泄。

It is not known whether ecallantide is excreted in human milk.

来源:Hazardous Substances Data Bank (HSDB)