CHIR-98014
作者：齐岳
发布时间：2023-08-29
13:38:19
点击数：
产品名称：CHIR-98014
产品描述：
| 产品描述 | CHIR-98014 is a selective GSK3 inhibitor; potentiate insulin activation of glucose transport and utilization in vitro and in vivo. |
| 靶点活性 | GSK-3α:0.65 nM, GSK-3β:0.58 nM |
| 体外活性 | CHIR 98014降低高血糖和改善葡萄糖利用的效果并不限于db/db小鼠和ZDF大鼠,由于观察到ob/ob小鼠,饮食诱导的糖尿病C57BL/6小鼠和用CHIR-2处理的葡萄糖不耐受的SHHF大鼠出现类似结果.此外,CHIR-98014降低了出生后大鼠皮质和海马中tau蛋白的磷酸化（Ser396）.GSK-3抑制剂CHIR-98014作用于从瘦弱的患有糖尿病和抗胰岛素的ZDF鼠分离的I型骨骼肌,激活GS活性.瘦弱患有糖尿病鼠分离的肌肉中,胰岛素和CHIR 98014激活的GS比ZDF鼠分离的肌肉中强很多.CHIR 98014或胰岛素作用于这些细胞和肌肉不会改变全部GS活性. 同时,CHIR 98014不会影响从瘦弱动物分离的肌肉中胰岛素剂量反应. |
| 体内活性 | 虽然CHIR-98014作为ATP结合的简单竞争性抑制剂,但它对GSK-3显示出相对于20种其他蛋白激酶（包括Cdc2,ERK2,Tie-2和KDR在内）500倍至> 1000倍的选择性。CHIR 98014抑制人类GSK-3β,Ki值为0.87 nM。CHIR 98014抑制CDC2,IC50为3.7 μM。然而,CHIR 98014对GSK-3高度同源的ɑ和β亚型具有相似效果,但是在GSK-3和接近的同系物cdc2和erk2间具有明显区别。CHIR 98014使CHO-IR和鼠肝细胞达到半数大GS刺激反应的浓度分别为106和107 nM。将表达胰岛素受体的CHO-IR细胞或原代大鼠肝细胞暴露于递增浓度的抑制剂CHIR98014中导致GS活性比率高于基础值的两倍至三倍的刺激。 |
| 激酶实验 | Kinase assays: Polypropylene 96-well plates are ?lled with 300 μL/well buffer (50 mM tris HCl, 10 mM MgCl2, 1 mM EGTA, 1 mM dithiothreitol, 25 mM β-glycerophosphate, 1 mM NaF, 0.01% BSA, pH 7.5) containing kinase, peptide substrate, and any activators. CHIR-98014 or controls are added in 3.5 μL of DMSO, followed by 50 μL of ATP stock to yield a ?nal concentration of 1 μM ATP in all cell-free assays. After incubation, triplicate 100-μL aliquots are transferred to Combiplate eight plates containing 100 μL/well 50 μM ATP and 20 mM EDTA. After 1 hour, the wells are rinsed ?ve times with PBS, ?lled with 200 μL of scintillation ?uid, sealed, left 30 min, and counted in a scintillation counter. All steps are performed at room temperature. |
| 细胞实验 | CHO-IR cells expressing human insulin receptor are grown to 80% con?uence in Hamm’s F12 medium with 10% fetal bovine serum and without hypoxanthine. Trypsinized cells are seeded in 6-well plates at 1 × 106 cells/well in 2 mL of medium without fetal bovine serum. After 24 hours, medium is replaced with 1 mL of serum-free medium containing GSK-3 inhibitor CHIR 98014 or control (?nal DMSO concentration 0.1%) for 30 min at 37 °C. Cells are lysed by freeze/thaw in 50 mM tris (pH 7.8) containing 1 mM EDTA, 1 mM DTT, 100 mM NaF, 1 mM phenylmethylsulfonyl ?uoride, and 25 μg/mL leupeptin (buffer A) and centrifuged 15 min at 4 °C/14000 g. The activity ratio of GS is calculated as the GS activity in the absence of glucose-6-phosphate divided by the activity in the presence of 5 mM glucose-6-phosphate. (Only for Reference) |
| 别名 | CHIR98014, CHIR 98014, CT98014 |
| 分子量 | 486.32 |
| 分子式 | C20H17Cl2N9O2 |
| CAS No. | 252935-94-7 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: <1 mg/mL
H2O: <1 mg/mL
DMSO: 8 mg/mL (16.45 mM),warmed
( < 1 mg/mL refers to the product slightly soluble or insoluble )
联系我们：
邮箱：2519696869@qq.com
QQ: 2519696869
电话：18066853083
微信：18066853083
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。
主营产品：COF、MOF单体系列：三蝶烯衍生物、金刚烷衍生物、四苯甲烷衍生物、peg、上转换、石墨烯、光电材料、点击化学、凝集素、载玻片、蛋白质交联剂、脂质体、蛋白、多肽、氨基酸、糖化学等。
