切换导航

CAL-101 (Idelalisib, GS-1101)

现货
Catalog No.
A3005
PI3K抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 600.00
现货
5mg
¥ 500.00
现货
20mg
¥ 1,100.00
现货
50mg
¥ 1,600.00
现货
100mg
¥ 2,650.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

CAL-101 (Idelalisib, GS-1101), is a p110δ selective phosphatidylinositol-3-kinase inhibitor in a kinome-wide screen using purified enzymes and in cell-based PI3K isoform-specific assays. Phosphatidylinositol-3-kinase p110δ serves as a central integration point for signaling from cell surface receptors known to promote malignant B-cell proliferation and survival. CAL-101 can block constitutive phosphatidylinositol-3-kinase signaling, resulting in reduced phosphorylation of Akt and other downstream effect factors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis. These effects have been observed across a broad range of immature and mature B-cell malignancies. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF-α, and fibronectin.

Reference

Brian J. Lannutti, Sarah A. Meadows, Sarah E. M. Herman, Adam Kashishian, Bart Steiner, Amy J. Johnson, John C. Byrd, Jeffrey W. Tyner, Marc M. Loriaux, Mike Deininger, Brian J. Druker, Kamal D. Puri, Roger G. Ulrich, and Neill A. Giese. CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011; 117(2): 591 – 594.

Sarah E. M. Herman, Amber L. Gordon, Amy J. Wagner, Nyla A. Heerema, Weiqiang Zhao, Joseph M. Flynn, Jeffrey Jones, Leslie Andritsos, Kamal D. Puri, Brian J. Lannutti, Neill A. Giese, Xiaoli Zhang, Lai Wei, John C. Byrd,  Amy J. Johnson. Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010; 116(12): 2078 – 88.

文献引用

1. Yaya Chu, Sanghoon Lee, et al. " Ibrutinib significantly inhibited Bruton’s tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model." OncoImmunology.11 Oct 2018.
2. Wensveen FM, Slinger E, et al. "Antigen-affinity controls pre-germinal centser B cell selection by promoting Mcl-1 induction through BAFF receptor signaling." Sci Rep. 2016 Oct 20;6:35673. PMID:27762293

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt415.43
Cas No.870281-82-6
FormulaC22H18FN7O
SynonymsCAL-101,CAL101,Idelalisib,GS-1101,GS1101
Solubility≥80.2 mg/mL in DMSO, <2.09 mg/mL in H2O, ≥2.1 mg/mL in EtOH with ultrasonic and warming
Chemical Name5-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-4-one
SDFDownload SDF
Canonical SMILESCCC(C1=NC2=C(C(=CC=C2)F)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

CD19/CD5阳性CLL细胞(> 90%)

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

< 5 μM:剂量依赖地抑制anti-IgM的促存活效应;= 5 μM,24h:抑制2.6%的anti-IgM活性;> 5 μM,72h:最大限度地减少CLL细胞的活力。

应用

CAL-101在较低剂量水平(< 5 μM)以剂量依赖的方式抑制anti-IgM的促存活效应。CAL-101在大于 5 μM浓度下处理72小时后最大限度地减少CLL细胞的活力。在5 μM浓度下处理24小时后,CAL-101显著减少了2.6%的anti-IgM的平均(SEM)促存活效应(92.7%)。

动物实验[2]:

动物模型

异种移植含有JAK2突变和/或CRLF2改变的从头(n=3)或复发(n=1)儿童Ph-样ALL样本的NOD-SCID-γ-null (NSG) 小鼠。

剂量

30 mg/kg/天,3天,口服给药。

应用

CAL101治疗可以有效抑制体内相关蛋白的磷酸化,包括磷酸化的(p)PI3K、mTOR、S6和AktS473,没有观察到其它已测蛋白磷酸化的增加,表明近端抑制有效抑制异常PI3K途径的信号转导,并诱导最小的补偿性信号上调。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Hoellenriegel J, Meadows S A, Sivina M, et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood, 2011, 118(13): 3603-3612.

[2] Li Y, Ryan T, Vincent T, et al. In vivo efficacy of PI3K pathway signaling inhibition for Philadelphia chromosome-like acute lymphoblastic leukemia. Blood, 2013, 122(21): 2672-2672.

生物活性

描述 CAL-101 (Idelalisib, GS-1101)是一个选择性的p110δ抑制剂,IC50值为2.5 nM。
靶点 p110δ          
IC50 2.5 nM          

质量控制

化学结构

CAL-101 (Idelalisib, GS-1101)

相关生物数据

CAL-101 (Idelalisib, GS-1101)

相关生物数据

CAL-101 (Idelalisib, GS-1101)

相关生物数据

CAL-101 (Idelalisib, GS-1101)