Ivermectin B1a

别名: 依维菌素;伊维菌素 B1a
目录号: V33655 纯度: ≥98%
伊维菌素B1a是阿维菌素B1a的类似物,是伊维菌素的主要成分。
Ivermectin B1a CAS号: 71827-03-7
产品类别: Parasite
产品仅用于科学研究,不针对患者销售
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产品描述
伊维菌素B1a是阿维菌素B1a的类似物,是伊维菌素的主要成分。伊维菌素 (MK-933) 是一种广谱抗寄生虫药。伊维菌素是一种用于对抗 SARS-CoV-2/COVID-19 的候选活性分子。
生物活性&实验参考方法
靶点
In invertebrates, the primary targets are glutamate-gated and gamma-aminobutyric acid (GABA)-gated chloride channels, leading to increased chloride ion conductance and subsequent paralysis in parasites. [2]
For its broad-spectrum antiviral activity, key targets include the inhibition of importin α/β-mediated nuclear transport, which affects the nuclear trafficking of viral proteins. Specific viral targets mentioned include the non-structural 3 helicase (NS3 helicase) of flaviviruses, the nuclear import of HIV-1 integrase and dengue virus NS5 polymerase, the nuclear import of UL42 protein of pseudorabies virus, and the nuclear localization signal-mediated import of the capsid protein (Cap) of porcine circovirus 2. [2]
体外研究 (In Vitro)
伊维菌素由伊维菌素B1a(不低于80%)和伊维菌素B1b(不超过20%)两种同源分子的混合物组成,是大环内酯类阿维菌素的成员。在剂量为 0.3 μg/ml 时,伊维菌素的主要成分伊维菌素 B1a 是惰性的,而在相同剂量下,次要成分伊维菌素 B1b 会导致蜗牛 100% 死亡[1]。
在0.3 μg/ml的浓度下,伊维菌素B1a对成年光滑双脐螺(Biomphalaria glabrata)无效,死亡率为0%。这与次要成分伊维菌素B1b形成对比,后者在相同浓度下导致100%的螺死亡。[1]
伊维菌素(该药物,其中伊维菌素B1a是主要成分)在体外对多种RNA和DNA病毒表现出广谱抗病毒活性。[2]
对于SARS-CoV-2,本文献引用的一项研究报告称,用伊维菌素处理受感染的Vero-hSLAM细胞后,48小时后病毒RNA减少了约5000倍。[2]
针对新城疫病毒,伊维菌素在100 μg/ml浓度下显示出强抗病毒活性,但在原代鸡成纤维细胞中表现出细胞毒性。[2]
体外抗病毒作用也有报道针对寨卡病毒、甲型流感病毒、西尼罗河病毒、委内瑞拉马脑炎病毒、猪繁殖与呼吸综合征病毒、基孔肯雅病毒、HIV-1、黄热病病毒、登革热病毒、日本脑炎病毒、蜱传脑炎病毒、伪狂犬病病毒、猪圆环病毒2型、细小病毒和牛疱疹病毒1型等。[2]
体内研究 (In Vivo)
伊维菌素的体内抗病毒潜力已有报道针对西尼罗河病毒和新城疫病毒。[2]
然而,在Ifnar1基因敲除小鼠模型中,伊维菌素未能有效预防致命的寨卡病毒感染。[2]
体内活性也有报道针对伪狂犬病病毒和细小病毒。[2]
药代性质 (ADME/PK)
吸收、分布和排泄
吸收良好。高脂餐可提高吸收率。
伊维菌素在肝脏代谢,其及其代谢物几乎全部经粪便排出,预计12天内完成,尿液中排泄的剂量不足给药剂量的1%。
分布容积为3~3.5 L/kg,且不透过血脑屏障。
代谢/代谢物
主要在肝脏代谢。伊维菌素及其代谢物几乎全部经粪便排出,预计12天内完成,尿液中排泄的剂量不足给药剂量的1%。
生物半衰期
口服后,伊维菌素的半衰期约为18小时。
毒性/毒理 (Toxicokinetics/TK)
肝毒性
单次服用伊维菌素治疗与血清转氨酶升高发生率较低相关。曾报道过一例使用伊维菌素后出现临床表现明显的肝损伤病例(病例1)。该病例在单次给药后1个月出现肝损伤,其特征为血清酶升高呈肝细胞型,但无黄疸。患者迅速完全康复。在伊维菌素预防 SARS-CoV-2 感染和改善早期及重症 COVID-19 病程的试验中,血清转氨酶升高并不罕见,但接受伊维菌素治疗的患者与接受安慰剂或对照药物治疗的患者相比,其发生率并无显著差异。
可能性评分:D(可能是导致轻度临床表现明显的肝损伤的罕见原因)。
蛋白质结合
93%
在针对光滑双脐螺(Biomphalaria glabrata)的杀螺活性测试中,浓度为 0.3 μg/ml 的伊维菌素 B1a未显示毒性,观察期内死亡率为 0%。[1]
参考文献

[1]. Ivermectin Efficacy Against Biomphalaria, Intermediate Host Snail Vectors of Schistosomiasis. J Antibiot (Tokyo). 2017 May;70(5):680-684.

[2]. Ivermectin, a New Candidate Therapeutic Against SARS-CoV-2/COVID-19. Ann Clin Microbiol Antimicrob. 2020 May 30;19(1):23.

其他信息
药效学
伊维菌素是一种半合成的驱虫药。它属于阿维菌素类,是一类源自土壤细菌阿维链霉菌(Streptomyces avermitilis)的五环十六元内酯(即大环内酯二糖)。阿维菌素类药物是强效广谱的抗寄生虫药。
伊维菌素B1a是市售伊维菌素的主要成分(约占80%),伊维菌素是一种抗寄生虫药物。[1]
它是阿维菌素B1a的22,23-二氢衍生物。 [1]
在这项评估伊维菌素对血吸虫病中间宿主螺类杀螺活性的研究中,发现伊维菌素B1a缺乏活性,而次要成分伊维菌素B1b被鉴定为导致螺类死亡的生物活性成分。[1]
伊维菌素B1a是伊维菌素的组成部分,伊维菌素是阿维菌素家族化合物的成员,由阿维链霉菌(Streptomyces avermitilis)产生。伊维菌素是阿维菌素B1的22,23-二氢衍生物。[2]
它是一种经美国食品药品监督管理局(FDA)批准的药物,广泛用于人和动物的驱虫和抗寄生虫治疗。[2]
其广谱抗病毒活性主要归因于其抑制核输入蛋白α/β介导的核转运的能力,从而阻断对病毒复制至关重要的病毒蛋白的核输入。 [2]
有人提议将其用于治疗 COVID-19,可能与羟氯喹联合使用,但其用于此适应症的临床疗效和安全性需要通过随机对照试验进行验证。[2]
由于制剂方面存在挑战,例如细胞毒性高和溶解度低,因此人们开始研究脂质体载体等递送系统以改善其特性。[2]
*注: 文献方法仅供参考, InvivoChem并未独立验证这些方法的准确性
化学信息 & 存储运输条件
分子式
C48H74O14
分子量
875.09
精确质量
874.508
CAS号
71827-03-7
PubChem CID
6321424
外观&性状
White to light yellow solid powder
LogP
5.601
tPSA
170.06
氢键供体(HBD)数目
3
氢键受体(HBA)数目
14
可旋转键数目(RBC)
8
重原子数目
62
分子复杂度/Complexity
1680
定义原子立体中心数目
20
SMILES
CC[C@H](C)[C@@H]1[C@H](CC[C@@]2(O1)C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([C@H](/C=C/C=C/4\CO[C@H]5[C@@]4([C@@H](C=C([C@H]5O)C)C(=O)O3)O)C)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O[C@H]7C[C@@H]([C@H]([C@@H](O7)C)O)OC)OC)\C)C
InChi Key
AZSNMRSAGSSBNP-XPNPUAGNSA-N
InChi Code
InChI=1S/C48H74O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3/b13-12+,27-15+,32-14+/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+/m0/s1
化学名
(1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-6'-[(2S)-butan-2-yl]-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one
HS Tariff Code
2934.99.9001
存储方式

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

运输条件
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
溶解度数据
溶解度 (体外实验)
DMSO : 100 mg/mL (114.27 mM)
溶解度 (体内实验)
配方 1 中的溶解度: ≥ 2.5 mg/mL (2.86 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中,混匀;然后向上述溶液中加入50 μL Tween-80,混匀;加入450 μL生理盐水定容至1 mL。
*生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。

配方 2 中的溶解度: ≥ 2.5 mg/mL (2.86 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

请根据您的实验动物和给药方式选择适当的溶解配方/方案:
1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL;

3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果,工作液请现配现用!
6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。
制备储备液 1 mg 5 mg 10 mg
1 mM 1.1427 mL 5.7137 mL 11.4274 mL
5 mM 0.2285 mL 1.1427 mL 2.2855 mL
10 mM 0.1143 mL 0.5714 mL 1.1427 mL

1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;

2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;

3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);

4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。

计算器

摩尔浓度计算器可计算特定溶液所需的质量、体积/浓度,具体如下:

  • 计算制备已知体积和浓度的溶液所需的化合物的质量
  • 计算将已知质量的化合物溶解到所需浓度所需的溶液体积
  • 计算特定体积中已知质量的化合物产生的溶液的浓度
使用摩尔浓度计算器计算摩尔浓度的示例如下所示:
假如化合物的分子量为350.26 g/mol,在5mL DMSO中制备10mM储备液所需的化合物的质量是多少?
  • 在分子量(MW)框中输入350.26
  • 在“浓度”框中输入10,然后选择正确的单位(mM)
  • 在“体积”框中输入5,然后选择正确的单位(mL)
  • 单击“计算”按钮
  • 答案17.513 mg出现在“质量”框中。以类似的方式,您可以计算体积和浓度。

稀释计算器可计算如何稀释已知浓度的储备液。例如,可以输入C1、C2和V2来计算V1,具体如下:

制备25毫升25μM溶液需要多少体积的10 mM储备溶液?
使用方程式C1V1=C2V2,其中C1=10mM,C2=25μM,V2=25 ml,V1未知:
  • 在C1框中输入10,然后选择正确的单位(mM)
  • 在C2框中输入25,然后选择正确的单位(μM)
  • 在V2框中输入25,然后选择正确的单位(mL)
  • 单击“计算”按钮
  • 答案62.5μL(0.1 ml)出现在V1框中
g/mol

分子量计算器可计算化合物的分子量 (摩尔质量)和元素组成,具体如下:

注:化学分子式大小写敏感:C12H18N3O4  c12h18n3o4
计算化合物摩尔质量(分子量)的说明:
  • 要计算化合物的分子量 (摩尔质量),请输入化学/分子式,然后单击“计算”按钮。
分子质量、分子量、摩尔质量和摩尔量的定义:
  • 分子质量(或分子量)是一种物质的一个分子的质量,用统一的原子质量单位(u)表示。(1u等于碳-12中一个原子质量的1/12)
  • 摩尔质量(摩尔重量)是一摩尔物质的质量,以g/mol表示。
/

配液计算器可计算将特定质量的产品配成特定浓度所需的溶剂体积 (配液体积)

  • 输入试剂的质量、所需的配液浓度以及正确的单位
  • 单击“计算”按钮
  • 答案显示在体积框中
动物体内实验配方计算器(澄清溶液)
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)
第二步:请输入动物体内配方组成(配方适用于不溶/难溶于水的化合物),不同的产品和批次配方组成不同,如对配方有疑问,可先联系我们提供正确的体内实验配方。此外,请注意这只是一个配方计算器,而不是特定产品的确切配方。
+
+
+

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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。

体内配方配制方法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 ddH2O,混匀澄清。

(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
            (2) 一定要按顺序加入溶剂 (助溶剂) 。

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Ivermectin Safety in Small Children
CTID: NCT04332068
Phase: Phase 2    Status: Recruiting
Date: 2024-05-21
COVID-OUT: Early Outpatient Treatment for SARS-CoV-2 Infection (COVID-19)
CTID: NCT04510194
Phase: Phase 3    Status: Completed
Date: 2024-05-16
Effect of Ivermectin Metabolites on Mosquito Survival
CTID: NCT03690453
Phase: Phase 4    Status: Completed
Date: 2024-04-24
Comparison Effectiveness of Oral Ivermectin , 1% Permethrin Shampoo and 4% Dimeticone Liquid Gel in the Treatment of Pediculosis Capitis Among School Children in Chachoengsao Province, Thailand
CTID: NCT06332872
Phase: Phase 4    Status: Active, not recruiting
Date: 2024-03-27
Emodepside Phase II Trial for Treatment of Onchocerciasis
CTID: NCT05180461
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-03-05
Oral Ivermectin for Chikungunya Viral Infection
CTID: NCT06259383
Phase: Phase 3    Status: Completed
Date: 2024-02-14
Repurposing Ivermectin for PKDL Treatment
CTID: NCT06251739
PhaseEarly Phase 1    Status: Recruiting
Date: 2024-02-09
Efficacy and Safety of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis
CTID: NCT04848688
Phase: Phase 3    Status: Completed
Date: 2024-01-25
Efficacy and Safety of MOX/ALB
A multicentre, phase III, double-blind, randomised, parallel, placebo-controlled trial to assess efficacy and safety of early administration of Ivermectin during 3 consecutive days to prevent SARS CoV-2 (COVID-19) hospitalisation in adults older than 50 years of age
CTID: null
Phase: Phase 3    Status: Prematurely Ended
Date: 2021-04-29
A randomized, double-blind, placebo-controlled study to assess the safety and efficacy of ivermectin in asymptomatic and mild severity COVID-19 patients
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2021-03-03
Investigation to assess the efficacy of benzyl benzoate 10/25% emulsion versus oral ivermectin for scabies treatment
CTID: null
Phase: Phase 4    Status: Ongoing
Date: 2020-12-17
Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the early Treatment of COVID-19
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2020-06-12
Pragmatic study 'CORIVER': Ivermectin as antiviral treatment for patients infected by SARS-COV2 (COVID-19)
CTID: null
Phase: Phase 3    Status: Ongoing
Date: 2020-06-02
Multicenter, randomized, double-blind, placebo-controlled study investigating efficacy, safety and tolerability of ivermectin HUVE-19 in patients with proven SARS-CoV-2 infection (COVID-19) and manifested clinical symptoms.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2020-05-15
Pilot study to evaluate the potential of ivermectin to reduce COVID-19 transmission
CTID: null
Phase: Phase 2    Status: Completed
Date: 2020-05-07
Evaluation of the potential anti-malarial effect of ivermectin: a controlled human malaria infection trial
CTID: null
Phase: Phase 2    Status: Completed
Date: 2018-04-20
Efficacy comparison of Ivermectin 1% topical cream associated with Doxycycline 40 mg Modified release (MR) capsules versus Ivermectin 1% topical cream associated with Placebo in the treatment of severe Rosacea.
CTID: null
Phase: Phase 3    Status: Completed
Date: 2017-06-15
Efficacy and safety of CD5024 1% in acne vulgaris
CTID: null
Phase: Phase 2    Status: Completed
Date: 2016-06-10
Randomized, Open-label, Multi Centre Phase III Clinical Trial on Multiple versus Single Dose of Ivermectin for the Treatment of Strongyloides
CTID: null
Phase: Phase 3    Status: GB - no longer in EU/EEA, Ongoing
Date: 2013-09-03
Efficacy and safety of CD5024 1% cream versus metronidazole 0.75% cream in subjects with papulopustular rosacea over 16 weeks treatment, followed by a 36-week extension period
CTID: null
Phase: Phase 3    Status: Completed
Date: 2012-03-12
A DOUBLE BLIND, VEHICLE CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE ACTIVITY OF CD5024 1% CREAM IN SUBJECTS WITH PAPULOPUSTULAR ROSACEA OVER 12 WEEKS TREATMENT
CTID: null
Phase: Phase 2    Status: Completed
Date: 2010-08-17
The effect of oral Ivermectin on Demodex associated blepharitis
CTID: null
Phase: Phase 4    Status: Prematurely Ended
Date: 2010-02-05
AN INVESTIGATOR BLIND PARALLEL GROUP VEHICLE CONTROL STUDY COMPARING THE EFFICACY AND SAFETY OF CD 5024 1% CREAM WITH METRONIDAZOLE 0.75% CREAM IN SUBJECTS WITH PAPULOPUSTULAR ROSACEA OVER 16 WEEKS TREATMENT
CTID: null
Phase: Phase 3    Status: Ongoing
Date: 2009-01-15
Plasma Pharmacokinetics study of CD5024 1% cream in subjects with papulopustular rosacea
CTID: null
Phase: Phase 2    Status: Completed
Date: 2008-07-04
A MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY AND EFFICACY OF CD5024 1% CREAM TREATMENT FOR UP TO 52 WEEKS IN SUBJECTS WITH PAPULOPUSTULAR ROSACEA
CTID: null
Phase: Phase 3    Status: Prematurely Ended, Completed
Date: 2008-07-04
ASSESSMENT OF THE EFFICACY AND SAFETY OF THREE CONCENTRATIONS: 1%, 0.3%, 0.1% OF CD5024 CREAM ONCE DAILY AND CD5024 1% CREAM TWICE DAILY, VERSUS ITS VEHICLE AND VERSUS METRONIDAZOLE 0.75% CREAM (ROZEX®), IN PATIENTS WITH PAPULO-PUSTULAR ROSACEA OVER 12 WEEKS
CTID: null
Phase: Phase 2    Status: Completed
Date: 2006-10-10
Randomized study on therapy of Strongyloides stercoralis invasion: ivermectine VS thiabendazole
CTID: null
Phase: Phase 3    Status: Completed
Date: 2004-11-03

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