XL019
作者：齐岳
发布时间：2023-08-28
09:02:42
点击数：
产品名称：XL019
产品描述：
| 产品描述 | XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1. |
| 靶点活性 | JAK2:2.2 nM |
| 体外活性 | XL019具有的药效学特性,并且表现出良好的口服吸收性,在不同物种中表现适中的清除率和半衰期.在给药30,100和300 mg/kg XL019后,明显抑制下游标记pSTAT1和pSTAT3,导致pSTAT1的ED 50为42 mg/kg和pSTAT3的ED 50为210 mg/kg.XL019抑制小鼠HEL.92.1.7异种移植生长,200 mg/kg和300 mg/kg XL019分别每天给药两次持续14天,表现60％和70％的抑制作用. |
| 体内活性 | L019抑制JAK2以及突变形式JAK2V617F的激活,其可导致JAK-STAT信号传导途径的抑制并可诱导凋亡。与其他细胞系统相比,在EPO刺激红细胞系后,XL019显示出10倍以上的STAT5磷酸化选择性抑制（IC50 = 64 nM）。 |
| 激酶实验 | FRET-Based Z′-Lyte Assay Detecting Peptide Substrate Phosphorylation: The kinases ABL1, ABL1(E255K), ABL1 (G250E), ABL1(T315I), and ABL1(Y253F) are P3049, PV3864, PV3865, PV3866, and PV3863 are full-length human recombinant protein expressed in insect cells and histidine-tagged. Inhibition activities of inhibitors against Abl1 and its mutants are performed in 384-well plates using the FRET-based Z′-Lyte assay system. Briefly, the kinase substrate is diluted into 5 μL of kinase reaction buffer; and the kinase is added. Compounds (10 nL) with indicated concentrations are then delivered to the reaction by using Echo liquid handler, and the mixture is incubated for 30 min at room temperature. Then 5 μL of 2X ATP solution is added to initiate the reaction, and the mixture is further incubated for 2 h at room temperature. The resulting reactions contains 10 μM (for wild-type Abl1, and mutants Y253F, Q252H, M351T, and H396P) or 5 μM (for mutants E255K, G250E, T315I) of ATP, 2 μM of Tyr2 Peptide substrate in 50 mM HEPES (PH 7.5), 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA, 0.0247 μg/mL Abl1, and inhibitors as appropriate. Then, 5 μL of development reagent is added, and the mixture is incubated for 2 h at room temperature before 5 μL of stop solution is added. Fluorescence signal ratio of 445 nm (Coumarin)/520 nm (fluorescin) is examined on an EnVision Multilabel Reader. The data are analyzed using Graphpad Prism5. The data are the mean value of three experiments. |
| 分子量 | 444.539 |
| 分子式 | C25H28N6O2 |
| CAS No. | 945755-56-6 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
DMSO: 13 mg/mL (29.2 mM)
Ethanol: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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公司介绍：
西安齐岳生物科技有限公司是集化学科研和定制与一体的高科技化学公司。业务范围包括化学试剂和产品的研发、生产、销售等。涉及产品为通用试剂的分销、非通用试剂的定制与研发，涵盖生物科技、化学品、中间体和化工材料等领域。
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