PCI-32765 (Ibrutinib)
(Synonyms: 伊布替尼; PCI-32765) 目录号 : GC13812
PCI-32765 (Ibrutinib) 是一种不可逆的选择性布鲁顿氏酪氨酸激酶 (BTK) 抑制剂，可选择性靶向其激酶结构域并通过降低其磷酸化能力来调节 BTK 下游信号传导，在无细胞试验中 IC50 为 0.5 nM 。
Cas No.:936563-96-1
Sample solution is provided at 25 µL, 10mM.
PCI-32765 (Ibrutinib) is an irreversible selective inhibitor of Bruton s tyrosine kinase (BTK) that selectively targets its kinase domain and modulates BTK downstream signaling by reducing its phosphorylating capacity with IC50 of 0.5 nM in cell-free assays [1,5,6]. Ibrutinib can cross the blood brain barrier, as shown in several preclinical reports[2]. As an immunomodulator, ibrutinib affects the function of peripheral innate and acquired immune cells, including macrophages,B cells,T cells, and natural killer cells[3,4].
Ibrutinib(1 µM;30 min) significantly reduced LPS-induced increases in proinflammatory cytokine levels in BV2 microglial cells. Ibrutinib also reduced LPS-induced BV2 microglial cell migration by inhibiting AKT signaling[4].Ibrutinib(1, 5, 10, 25, or 50 µmol/L for 24h) improved the decreased cell viability and attenuated oxidative stress in the high glucose incubated PC12 cells which subjected to H/R injury[8].
Ibrutinib(50 mg/kg/day; p.o.; 5 days) treatment significantly improved the immobility time, body weight, and sucrose preference induced by LPS, suggesting the antidepressant potential of ibrutinib[7]. Ibrutinib(50 mg/kg/d; i.g.) significantly inhibited the expression of pyroptosis related proteins (NLRP3, Caspase-1, Gasdermin D (GSDMD), IL-1β and IL-18) in the lung tissues of sepsis mice[9].
References:
[1]. de Porto AP, Liu Z, et,al. Btk inhibitor ibrutinib reduces inflammatory myeloid cell responses in the lung during murine pneumococcal pneumonia. Mol Med. 2019 Jan 15;25(1):3. doi: 10.1186/s10020-018-0069-7. PMID: 30646846; PMCID: PMC6332549.
[2]. Goldwirt L, Beccaria K, et,al. Ibrutinib brain distribution: a preclinical study. Cancer Chemother Pharmacol. 2018 Apr;81(4):783-789. doi: 10.1007/s00280-018-3546-3. Epub 2018 Feb 23. PMID: 29476222.
[3]. Grommes C, Pastore A, et,al. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discov. 2017 Sep;7(9):1018-1029. doi: 10.1158/2159-8290.CD-17-0613. Epub 2017 Jun 15. PMID: 28619981; PMCID: PMC5581705.
[4]. Nam HY, Nam JH, et,al. Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice. J Neuroinflammation. 2018 Sep 19;15(1):271. doi: 10.1186/s12974-018-1308-0. PMID: 30231870; PMCID: PMC6145206.
[5]. Burger JA, Buggy JJ. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765). Leuk Lymphoma. 2013 Nov;54(11):2385-91. doi: 10.3109/10428194.2013.777837. Epub 2013 Aug 28. PMID: 23425038.
[6]. Honigberg LA, Smith AM, et,al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80. doi: 10.1073/pnas.1004594107. Epub 2010 Jul 6. PMID: 20615965; PMCID: PMC2919935.
[7]. Li W, Ali T, et,al. Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression. Brain Behav Immun. 2021 Feb;92:10-24. doi: 10.1016/j.bbi.2020.11.008. Epub 2020 Nov 10. PMID: 33181270.
[8]. Jin L, Mo Y, et,al. Ibrutinib ameliorates cerebral ischemia/reperfusion injury through autophagy activation and PI3K/Akt/mTOR signaling pathway in diabetic mice. Bioengineered. 2021 Dec;12(1):7432-7445. doi: 10.1080/21655979.2021.1974810. PMID: 34605340; PMCID: PMC8806753.
[9]. Tang H, Li H, et,al. Ibrutinib protects against acute lung injury via inhibiting NLRP3/Caspase-1 in septic mice model. Mol Immunol. 2022 Dec;152:232-239. doi: 10.1016/j.molimm.2022.11.006. Epub 2022 Nov 12. PMID: 36379131.
PCI-32765 (Ibrutinib) 是一种不可逆的选择性布鲁顿氏酪氨酸激酶 (BTK) 抑制剂，可选择性靶向其激酶结构域并通过降低其磷酸化能力来调节 BTK 下游信号传导，在无细胞试验中 IC50 为 0.5 nM [1 ,5,6]。伊布替尼可以穿过血脑屏障，如多个临床前报告所示[2]。作为一种免疫调节剂，伊布替尼影响外周先天性和获得性免疫细胞的功能，包括巨噬细胞、B 细胞、T 细胞和自然杀伤细胞[3,4]。
Ibrutinib（1 µ；M；30 分钟）显着降低 BV2 小胶质细胞中 LPS 诱导的促炎细胞因子水平升高。 Ibrutinib 还通过抑制 AKT 信号转导减少 LPS 诱导的 BV2 小胶质细胞迁移[4]。Ibrutinib（1、5、10、25 或 50 µ；mol/L 持续 24 小时）改善细胞活力降低并减弱氧化应激在高葡萄糖孵育 H/R 损伤的 PC12 细胞[8]。
Ibrutinib（50 mg/kg/天；口服；5 天）处理显着改善不动时间、体重和诱导的蔗糖偏好LPS，表明依鲁替尼的抗抑郁潜力[7]。 Ibrutinib（50 mg/kg/d；i.g）显着抑制脓毒症小鼠肺组织中细胞焦亡相关蛋白（NLRP3、Caspase-1、Gasdermin D (GSDMD)、IL-1β；和 IL-18）的表达[9] ].
| Cell experiment [1]: | |
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Cell lines |
BV2 microglial cells |
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Preparation Method |
Cells were treated with PCI-32765 (Ibrutinib) (1 µM) or vehicle (1% DMSO), followed by lipopolysaccharide (LPS; 1 µg/ml) or PBS. RT-PCR, immunocytochemistry, and subcellular fractionation were performed to examine the effects of ibrutinib on neuroinflammatory responses. |
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Reaction Conditions |
1 µM;30 min |
|
Applications |
Ibrutinib significantly reduced LPS-induced increases in proinflammatory cytokine levels in BV2 microglial cells. Ibrutinib also reduced LPS-induced BV2 microglial cell migration by inhibiting AKT signaling. |
| Animal experiment [2]: | |
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Animal models |
Adult C57BL/6J male mice weighing 25-30g (age 12-14 weeks) |
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Preparation Method |
The experimental animals were divided into four groups (each group = 10 animals): normal saline-treated (NC), LPS (2 mg/kg/day) treated (LPS), LPS + Ibrutinib (50 mg/kg/day) treated (LPS + IBR), and Ibrutinib (50 mg/kg/day) treated (IBR). |
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Dosage form |
50 mg/kg/day; p.o.; 5 days |
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Applications |
Ibrutinib attenuated LPS-induced depressive-like behaviors. |
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References: [1].Nam HY, Nam JH, et,al. Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice. J Neuroinflammation. 2018 Sep 19;15(1):271. doi: 10.1186/s12974-018-1308-0. PMID: 30231870; PMCID: PMC6145206. | |
| Cas No. | 936563-96-1 | SDF | |
| 别名 | 伊布替尼; PCI-32765 | ||
| 化学名 | 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide | ||
| Canonical SMILES | C=CC(=O)N1CCCC(C1)N2C3=C(C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)C(=NC=N3)N | ||
| 分子式 | C25H24N6O2 | 分子量 | 440.5 |
| 溶解度 | ≥ 22.025mg/mL in DMSO | 储存条件 | 4°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 | 2.2701 mL | 11.3507 mL | 22.7015 mL |
| 5 mM | 0.454 mL | 2.2701 mL | 4.5403 mL |
| 10 mM | 0.227 mL | 1.1351 mL | 2.2701 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。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
