Ibrutinib (PCI-32765)
目录号：S2680
Molecular Weight(MW): 440.5
Ibrutinib (PCI-32765)是一种有效的，高选择性的Brutons tyrosine kinase (Btk)抑制剂，无细胞试验中IC50为0.5 nM，对Bmx， CSK， FGR， BRK及HCK适度有效，对EGFR， Yes， ErbB2， JAK3等作用效果较弱。
客户使用该产品的9个实验数据：
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Autoproliferation of B and CD4+ T cells upon addition of the selective BTK inhibitor ibrutinib or vehicle (DMSO) control (left graph). Right graph shows the HLA-DR expression (line) and survival (numbers) of B cells (mean ± SEM; n = 3 REM).
Cell, 2018, 175(1):85-100. Ibrutinib (PCI-32765) purchased from Selleck.
BTK C481S and C481T variants show resistance to ibrutinib. (a and b) COS-7 cells were transfected with wild-type BTK or the two variants. Thirty-six hours post transfection, the cells were serum starved and treated with ibrutinib overnight followed by activation with serum and pervanadate for 5 min at room temperature. The cell lysates were immunoblotted for pY223 BTK and pY753 PLCγ2.
Leukemia, 2017, 31(1):177-185. Ibrutinib (PCI-32765) purchased from Selleck.
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Cell lines were exposed to 0, 50 and 150 mM Ibrutinib for 4 h. The level of phosphorylated ERK1/2 (p-ERK1/2) was reduced in TCF3-rearranged MHH-CALL3 compared with non-TCF3-rearranged Nalm6 and MHH-CALL4 cell lines. b-Actin served as a loading control. P-ERK/b-actin: ratio of the intensities. See Supplementary Materials and methods document for more information.
Blood Cancer J 2014 4, e181. Ibrutinib (PCI-32765) purchased from Selleck.
Phosphorylation of ERK1/2 and AKT, but not BTK, was inhibited in sensitive but not resistant MCL cells. Western blotting of BTK phosphorylation. Mantle cell lymphoma (MCL) cells were treated with indicated doses of ibrutinib, cell lysates were collected at 1 or 4 h, and subjected to Western blotting analysis using phosphorylated BTK (p-BTK) (Y223) and total BTK (t-BTK) antibodies.
Br J Haematol 2014 166(6), 849-61. Ibrutinib (PCI-32765) purchased from Selleck.
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Identification of Btk as a potent kinase for WIP tyrosine phosphorylation. Total protein lysates were prepared from THP-1 cells that were stably transfected with wild-type WIP-EGFP and treated with PCI-32765 at the concentration specified on the blots for 2h before pervanadate treatment for 30 min. In all cases WIP-EGFP was immunoprecipitated from cell lysates using anti-EGFP antibody and membranes subsequently blotted with the pY (4G10) antibody, EGFP antibody and β-Tubulin.
J Cell Sci 2015 128(2), 251-65. Ibrutinib (PCI-32765) purchased from Selleck.
Effect of Ibrutinib on CLEC-2-mediated platelet activation and signaling in humans. Washed human platelets were incubated with Ibrutinib (5 nM) for 5 min followed by stimulation with convulxin (100 ng/ml) or rhodocytin (30 nM) under stirred conditions. Platelet proteins were separated by SDS-PAGE, Western-blotted, and probed for phospho Syk (Tyr525/526) and PLCγ2 (Tyr759). β-actin was used as a lane loading control.
J Biol Chem 2015 290(18), 11557-68. Ibrutinib (PCI-32765) purchased from Selleck.
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BTK is expressed by malignant plasma cells and ibrutinib induces cytotoxicity in MM patient cells. (A) BTK mRNA and protein expression in control B-cells and MM patient cells and MM cell lines as measured by real-time PCR and Western blotting. (B) MM cells (n = 11) were treated with two doses of ibrutinib (1 and 10 μM), bortezomib (10 and 20 nM) and lenalidomide (1 and 10 μM) for 48 h and then assessed for cell death/proliferation by Cell Titer GLO assay. (C and D) MM cell lines were analysed for cell death in response to ibrutinib (1 and 10 μM), bortezomib (10 and 20 nM) and lenalidomide.
Cell Signal 2013 25, 106-12. Ibrutinib (PCI-32765) purchased from Selleck.
Ibrutinib induces increased cytotoxicity in combination with lenalidomide and bortezomib in MM patient cells. (A) MM patient cells were treated wit h various combinations of ibrutinib (1 and 10 μM), bortezomib (10 and 20 nM) and lenalidomide (1 and 10 μM) for 48 h and then assessed for cell death/proliferation by Cell Titer GLO assay. (B) MM cell lines were analysed for cell death in response to various combinations of ibrutinib (1 and 10μM), bortezomib (10 and 20 nM) and lenalidomide. (C) RPMI8226 cells were analysed for cell death in response to ibrutinib (1 and 10μM), bortezomib (20 nM) and lenalidomide (10μM) and combinations thereof, and then analysed for apoptosis using annexin-V/propidium iodide staining and flow cytometry. (D) Primary human monocytes were treated with two doses of ibrutinib (1 and 10 μM) and then in combination with bortezomib (20 nM) and lenalidomide (10 μM) for 48 h and then assessed for cell death/proliferation by Cell Titer GLO assay.
Cell Signal 2013 25, 106-12. Ibrutinib (PCI-32765) purchased from Selleck.
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Ibrutinib downregulates anti-apoptotic proteins and induces caspase mediated apoptosis in MM cells. (A) FLIPL , survivin and Bcl- xL mRNA expression was determined in MM patient cells and MM cell lines treated with ibrutinib (10 μM) and bortezomib (20 nM) both alone and in combination. (B) FLIPL protein expression was measured by Western blotting in extracts from RPMI8226 cells treated with ibrutinib (10μM) and bortezomib (20 nM) both alone and in combination for 8 hours. (C) The MM cell line RPMI8226 was treated with the pan caspase inhibitor zVAD-fmk (10 μM) before treatment with ibrutinib (10 μM) and borte zomib (20 nM) both alone and in combination for 48 h and then assessed for cell death/prolife ration by Cell Titer GLO assay.
Cell Signal 2013 25, 106-12. Ibrutinib (PCI-32765) purchased from Selleck.
产品安全说明书
BTK抑制剂选择性比较
生物活性
| 产品描述 | Ibrutinib (PCI-32765)是一种有效的，高选择性的Brutons tyrosine kinase (Btk)抑制剂，无细胞试验中IC50为0.5 nM，对Bmx， CSK， FGR， BRK及HCK适度有效，对EGFR， Yes， ErbB2， JAK3等作用效果较弱。 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 体外研究 |
Ibrutinib有效可逆且选择性抑制Btk酶活性。Ibrutinib作用于 BCR 通路激活的 DOHH2细胞系, 抑制Btk自磷酸化, Btk's 生理底物 PLCγ磷酸化, 和更远一点的下游激酶ERK的磷酸化，IC50分别为11 nM, 29 nM 和 13 nM。[1] Ibrutinib作用于慢性淋巴细胞白血病 (CLL) 细胞，诱导细胞毒性，这种作用存在剂量和时间依赖性。此外, Ibrutinib诱导 caspase依赖性细胞死亡通路激活，且在TLR信号后，抑制CLL细胞增殖能力。[2] 最新研究显示Ibrutinib抑制 BCR激活的原代 B细胞增殖,IC50 为8 nM，且抑制 原代单核细胞中TNFα, IL-1β 和 IL-6产量， IC50 分别为2.6 nM, 0.5 nM, 和 3.9 nM。 [3] |
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| 体内研究 | Ibrutinib 作用于胶原诱导的关节炎模型，通过抑制B细胞活性，显著降低足肿胀和关节发炎等临床关节炎症状。Ibrutinib 作用于 MRL-Fas(lpr) 狼疮模型 ,降低肾疾病和自身抗体产量。[1] Ibrutinib 每天按25 mg/kg剂量作用于过继转移TCL1 的CLL小鼠模型, 产生短暂的早期淋巴细胞增多症，且延迟CLL 疾病进展。[4] |
推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
| 激酶实验：[1] |
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激酶实验: 激酶, 33P-ATP, Ibrutinib, 和底物 [0.2 mg/mL 聚(EY)(4:1)]温育1小时后，使用33P 过滤结合实验测量体外激酶IC50值。 |
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| 细胞实验：[2] |
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| 动物实验：[2] |
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溶解度 (25°C)
| 体外 | DMSO | 88 mg/mL (199.77 mM) |
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| Ethanol | 45 mg/mL (102.15 mM) | |
| Water | Insoluble | |
| 体内 |
从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 5% DMSO+30% PEG 300+5% Tween 80+ddH2O |
10mg/mL |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 440.5 |
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| 化学式 | C25H24N6O2 |
| CAS号 | 936563-96-1 |
| 稳定性 | powder |
| in solvent | |
| 别名 | N/A |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT03873493 | Not yet recruiting | Leukemia|T-cell Prolymphocytic Leukemia (T-PLL)|Cancer | AbbVie | June 6 2019 | Phase 2 |
| NCT03873493 | Not yet recruiting | Leukemia|T-cell Prolymphocytic Leukemia (T-PLL)|Cancer | AbbVie | June 6 2019 | Phase 2 |
| NCT03514017 | Not yet recruiting | Chronic Lymphocytic Leukemia | H. Lee Moffitt Cancer Center and Research Institute|Merck Sharp & Dohme Corp.|Janssen Scientific Affairs LLC | May 2019 | Phase 2 |
| NCT03514017 | Not yet recruiting | Chronic Lymphocytic Leukemia | H. Lee Moffitt Cancer Center and Research Institute|Merck Sharp & Dohme Corp.|Janssen Scientific Affairs LLC | May 2019 | Phase 2 |
| NCT03697512 | Not yet recruiting | Marginal Zone Lymphoma|Nodal Marginal Zone Lymphoma|Splenic Marginal Zone Lymphoma | International Extranodal Lymphoma Study Group (IELSG) | April 15 2019 | Phase 2 |
| NCT03513562 | Not yet recruiting | Chronic Lymphocytic Leukemia|Ibrutinib Resistance | Ohio State University Comprehensive Cancer Center|National Cancer Institute (NCI) | April 30 2019 | Phase 2 |
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常见问题及建议解决方法
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问题 1：
How to reconstitute the compound S2680 for in vivo studies?
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回答：
For in vivo study, we suggest to use 5% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 10mg/ml.
