| CAS |
No.936563-96-1 |
| 中文名称 |
依鲁替尼(10mM in DMSO,无菌） |
| 英文名称 |
Ibrutinib(10mM in DMSO，Sterile） |
| 分子式 |
C25H24N6O2 |
| 分子量 |
440.5 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 运输条件 |
冷冻运输 |
| 靶点 |
Btk |
| 通路 |
Protein Tyrosine Kinase/RTK;Angiogenesis |
| 背景说明 |
依鲁替尼是一种小分子的 BTK 抑制剂，可与BTK 活性位点上的半胱氨酸残基( Cys-481)选择性地共价结合，不可逆地抑制 BTK 的活性，进而抑制 BCR 信号通路的激活。 |
| 生物活性 |
Ibrutinib (PCI-32765) is a selective， irreversible Btk inhibitor with an IC50 of 0.5 nM.[1-4] |
| IC50 |
IC50:0.5nM (Btk)[4] |
| In Vitro |
Ibrutinib (PCI-32765) selectively inhibits B-cell signaling and activation. It inhibits autophosphorylation of Btk (IC50=11 nM)， phosphorylation of Btk‘s physiological substrate PLCγ (IC50=29 nM)， and phosphorylation of a further downstream kinase， ERK (IC50=13 nM)[1].Ibrutinib (PCI-32765) inhibits BCR-activated primary B cell proliferation (IC50=8 nM). Following FcγR stimulation， Ibrutinib (PCI-32765) inhibits TNFα， IL-1β and IL-6 production in primary monocytes (IC50=2.6， 0.5， 3.9 nM， respectively)[3].Ibrutinib binds C481 (Cysteine481) of BTK with an ideal IC50 of 0.5?nM. Ibrutinib cannot form a covalent bond with the hydroxyl group of serine， C481S mutation increases the IC50 against BTK-C481S phosphorylation from 2.2?nM to 1?μM[4]. |
| In Vivo |
Ibrutinib (PCI-32765) (3.125-50 mg/kg， p.o.) reduces the level of circulating autoantibodies and completely suppresses disease in mice with collagen-induced arthritis. Ibrutinib (PCI-32765) inhibits autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Ibrutinib (PCI-32765) (3.125-50 mg/kg， p.o.) reduces renal disease and autoantibody production in MRL-Fas(lpr) mice[1]. Ibrutinib (PCI-32765) (0.1 μM) inhibits activation-induced proliferation of CLL cells， induces selective cytotoxicity in B cells compared with T cells， but alters activation induced T-cell cytokine production[2]. Ibrutinib (PCI-32765) dose-dependently and potently reverses arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. Ibrutinib (PCI-32765) also prevents clinical arthritis in CAIA models[3]. |
| 细胞实验 |
Primary human B cells are isolated from peripheral blood mononuclear cell using human Miltenyl human B cell Isolation Kit II. In 0.2 mL RPMI plus 10% FBS， 100，000 B cells are treated with Ibrutinib (PCI-32765) (0.3 nM-10 μM) in triplicate wells or vehicle control in 0.1% DMSO final concentration for 30 minutes at 37°C， 5% CO2， then cells are stimulated with 10 μg/mL anti-IgM F(ab‘)2， 5 μg/mL anti-CD3/CD28 as a negative control or 0.5 μg/mL PMA (Phorbal 12-myristate 13-acetate) as a positive control. B cells are stimulated for 72 hours at 37°C， 5% CO2. Proliferation is measured with Cell Titer Glo reagent and measured on a luminometer.[1-4] |
| 动物实验 |
Male DBA1/1OlaHsd mice are injected on days 0 and 21 with Freunds‘ Complete Adjuvant containing bovine type II collagen. On days 21 to 35， mice are randomized into treatment groups when the average clinical score of each animal is 1.5 (in a scale of 5). Ibrutinib (PCI-32765) treatment (1.56-12.5 mg/kg， p.o.) is initiated following enrollment and continues for 18 days. Clinical scores are given to each mouse daily for each paw. Clinical score assessment is made using the following criteria: 0=normal; 1=one hind paw or fore paw joint affected or minimal diffuse erythema and swelling; 2=two hind or fore paw joints affected or mild diffuse erythema and swelling; 3=three hind or fore paw joints affected or moderate diffuse erythema and swelling; 4=marked diffuse erythema and swelling or four digit joints affected; 5=severe diffuse erythema and severe swelling of entire paw， unable to flex digits.[1-4] |
| 数据来源文献 |
[1]. Honigberg LA， 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]. Herman SE， et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011 Jun 9;117(23):6287-96.
[3]. Chang BY， et al. The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011 Jul 13;13(4):R115.
[4]. Sun Y， et al. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Res. 2018 Jul;28(7):779-781. |
| 规格 |
1ml |
| 单位 |
瓶 |
中文
英语
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