store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
CHZ868 是II型 JAK 抑制剂,具有潜在的抗肿瘤活性,可逆转 I 型 JAK 抑制剂的持续存在,可用于研究白血病。
产品描述 | CHZ868 is a type II JAK inhibitor with potential antitumor activity that reverses the persistence of type I JAK inhibitors and can be used to study leukemia. |
靶点活性 | JAK2:110 nM, CMK cells:378 nM (GI50), SET2 cells:59 nM (GI50) |
体外活性 | CHZ868 effectively inhibits constitutive phosphorylation of JAK2 and STAT5 in JAK2V617F SET2 cells. The compound demonstrates potent inhibition of SET2 cell proliferation (GI50=59nM) and exhibits 6-fold lower growth inhibitory activity against CMK cells (GI50=378nM)[1]. At a concentration of 100 nM, CHZ868 shows activity against 26 kinases, including JAK2 and TYK2. It is believed that CHZ868 interacts with the hinge region of JAK2 through two hydrogen bonds, formed between the amino-pyridine of CHZ868 and the backbone-NH/CO of L932, while the pyridine occupies the adenine pocket of the ATP binding site. CHZ868 effectively suppresses the growth of CRLF2-rearranged human B-ALL cells and disrupts JAK2 signaling[1]. |
体内活性 | Characterized by high passive permeability, good metabolic stability, and low water solubility, CHZ868 also exhibits moderate blood clearance and good oral bioavailability, rendering it suitable for in vivo applications. In mice with human or murine B-ALL, CHZ868 enhances survival. When used in combination with dexamethasone, CHZ868 synergistically induces apoptosis in JAK2-dependent B-ALLs, leading to improved survival compared to CHZ868 alone[1]. |
细胞实验 | CHZ868 is dissolved in DMSO to make 10 mM stock solution and diluted in culture media. Cells are treated with CHZ868 (0, 0.05, 0.1, 0.2 μM) or vehicle (DMSO). After 48 hr (Ba/F3 cells) or 72 hr (MHH-CALL4 and PDX cells), CellTiter-Glo Luminescent Cell Viability Assay is added (10 μL undiluted or 25 μL of a 1:2 dilution in each well) and plates are read [2]. |
动物实验 | CHZ868 is reconstituted in 0.5% methylcellulose / 0.5% Tween-80 and administered at doses of 10 or 30 mg/kg/day by oral gavage. Pharmacokinetic/pharmacodynamic and efficacy studies in the mouse model of rhEpo-induced polycythemia are carried out essentially. Detection of STAT5 phosphorylation in spleen lysates by Meso Scale Discovery is performed [2]. |
分子量 | 423.42 |
分子式 | C22H19F2N5O2 |
CAS No. | 1895895-38-1 |
store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 50 mg/mL (118.08 mM), Sonication is recommended.
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.3617 mL | 11.8086 mL | 23.6172 mL | 59.043 mL |
5 mM | 0.4723 mL | 2.3617 mL | 4.7234 mL | 11.8086 mL | |
10 mM | 0.2362 mL | 1.1809 mL | 2.3617 mL | 5.9043 mL | |
20 mM | 0.1181 mL | 0.5904 mL | 1.1809 mL | 2.9522 mL | |
50 mM | 0.0472 mL | 0.2362 mL | 0.4723 mL | 1.1809 mL | |
100 mM | 0.0236 mL | 0.1181 mL | 0.2362 mL | 0.5904 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
CHZ868 1895895-38-1 Angiogenesis Chromatin/Epigenetic JAK/STAT signaling Stem Cells JAK CHZ-868 CHZ 868 Inhibitor inhibitor inhibit