产品说明书

Ibrutinib

Print
Chemical Structure| 936563-96-1 同义名 : 依鲁替尼 ;PCI-32765;Imbruvica;PCI32765, PCI-32765, PCI 32765, Ibrutinib, Imbruvica
CAS号 : 936563-96-1
货号 : A150396
分子式 : C25H24N6O2
纯度 : 98%
分子量 : 440.497
MDL号 : MFCD20261150
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(238.37 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 12 mg/mL clear

PO 0.5% CMC-Na 35 mg/mL suspension

生物活性
靶点

  • BTK

    BTK, IC50:0.5 nM
描述 Btk (Bruton tyrosine kinase), a non-receptor tyrosine kinase, is specifically required for BCR signaling which contributes to the initiation and maintenance of B-cell malignancies and autoimmune diseases. Ibrutinib, also called as PCI-32765 or imbruvica, is a potent Btk inhibitor with IC50 of 0.5 nM (measured by 33P filtration binding assay), modestly potent to Blk (IC50= 0.5 nM), Bmx (IC50= 0.8 nM), CSK (IC50= 2.3 nM), FGR (IC50= 2.3 nM), BRK (IC50= 3.3 nM), HCK (IC50= 3.7 nM), less potent to EGFR (IC50= 5.6 nM), Yes (IC50= 6.5 nM), ErbB2 (IC50= 9.4 nM), ITK (IC50= 10.7 nM). Ibrutinib can selectively inhibit B-cell signaling and activation, including inhibition of autophosphorylation of Btk, phosphorylation of Btk's physiological substrate PLCγ and phosphorylation of a further downstream kinase ERK, in DOHH2 cells. Continuous exposure to 10 nM Ibrutinib for 18h completely prevented up-regulation of CD69, the B-cell activation marker. In vivo study shows that Btk inhibition by Ibrutinib is efficacious for autoimmune disease animal model. Oral treatment daily for 11 days with 12.5 mg/kg of Ibrutinib can inhibit collagen-induced arthritis in mice[1]. Up to now, Ibrutinib is approved to the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, small lymphocytic lymphoma, marginal zone lymphoma, and chronic graft versus host disease[2].
作用机制 Ibrutinib can bind covalently to a cysteine residue (Cys-481) in the active site, leading to potent and irreversible inhibition of Btk enzymatic activity[3]. Notice: BMX, EGFR, ErbB2, ITK, JAK3,AK3 and TEC is the kinase that contains a cysteine residue aligning with Cys-481 same as Btk, resulting in the binding with Ibrutinib[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human DOHH2 cells Cytotoxic assay 72 h Cytotoxicity against human DOHH2 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50=0.41 μM. 24915291
human Pfeiffer cells Function assay 72 h Cytotoxicity against human Pfeiffer cells assessed as growth inhibition after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50=2 nM. 24915291
human Ramos cells Function assay 1 h Inhibition of Btk in human Ramos cells assessed as inhibition of PLC-gamma2 phosphorylation at Tyr1217 after 1 hr by Western blot analysis, IC50=14 nM. 24915291
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02824029 Classical Hodgkin Lymphoma ... 展开 >> Recurrent Hodgkin Lymphoma Refractory Hodgkin Lymphoma 收起 << Phase 2 Recruiting February 2019 United States, Michigan ... 展开 >> Wayne State University/Karmanos Cancer Institute Recruiting Detroit, Michigan, United States, 48201 Contact: Radhakrishnan Ramchandren    313-576-8739       Principal Investigator: Radhakrishnan Ramchandren, M.D.          Sub-Investigator: Divaya Bhutani, M.D.          Sub-Investigator: Jay Yang, M.D.          Sub-Investigator: Jeffrey Zonder, M.D.          Sub-Investigator: Charles Schiffer, M.D.          Sub-Investigator: Abhinav Deol, M.D.          United States, Texas M D Anderson Cancer Center Not yet recruiting Houston, Texas, United States, 77030 Contact: Michelle A. Fanale    713-792-2860    mfanale@mdanderson.org    Principal Investigator: Michelle A. Fanale 收起 <<
NCT03021460 Metastatic Melanoma ... 展开 >> Stage III Skin Melanoma Stage IIIA Skin Melanoma Stage IIIB Skin Melanoma Stage IIIC Skin Melanoma Stage IV Skin Melanoma 收起 << Phase 2 Recruiting February 1, 2021 United States, Minnesota ... 展开 >> Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Matthew S. Block 收起 <<
NCT02899078 Metastatic Renal Cell Cancer ... 展开 >> Stage IV Renal Cell Cancer 收起 << Phase 1 Phase 2 Recruiting May 2020 United States, California ... 展开 >> University of California Davis Comprehensive Cancer Center Recruiting Sacramento, California, United States, 95817 Contact: Primo N. Lara, M.D.    916-734-3771    pnlara@ucdavis.edu    Principal Investigator: Primo N. Lara, M.D.          Sub-Investigator: Chong-Xian Pan, M.D., Ph.D. 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.27mL

0.45mL

0.23mL

11.35mL

2.27mL

1.14mL

22.70mL

4.54mL

2.27mL
参考文献

[1]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.

[2]Pan Z, Scheerens H, et al. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem. 2007 Jan;2(1):58-61.