CHIR-98014
作者：齊岳
發布時間：2023-08-29
13:38:19
點擊數：
產品名稱：CHIR-98014
產品描述：
| 產品描述 | CHIR-98014 is a selective GSK3 inhibitor; potentiate insulin activation of glucose transport and utilization in vitro and in vivo. |
| 靶點活性 | GSK-3α:0.65 nM, GSK-3β:0.58 nM |
| 體外活性 | 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,由于觀察到ob/ob小鼠,飲食誘導的糖尿病C57BL/6小鼠和用CHIR-2處理的葡萄糖不耐受的SHHF大鼠出現類似結果.此外,CHIR-98014降低了出生后大鼠皮質和海馬中tau蛋白的磷酸化（Ser396）.GSK-3抑制劑CHIR-98014作用于從瘦弱的患有糖尿病和抗胰島素的ZDF鼠分離的I型骨骼肌,激活GS活性.瘦弱患有糖尿病鼠分離的肌肉中,胰島素和CHIR 98014激活的GS比ZDF鼠分離的肌肉中強很多.CHIR 98014或胰島素作用于這些細胞和肌肉不會改變全部GS活性. 同時,CHIR 98014不會影響從瘦弱動物分離的肌肉中胰島素劑量反應. |
| 體內活性 | 雖然CHIR-98014作為ATP結合的簡單競爭性抑制劑,但它對GSK-3顯示出相對于20種其他蛋白激酶（包括Cdc2,ERK2,Tie-2和KDR在內）500倍至> 1000倍的選擇性。CHIR 98014抑制人類GSK-3β,Ki值為0.87 nM。CHIR 98014抑制CDC2,IC50為3.7 μM。然而,CHIR 98014對GSK-3高度同源的ɑ和β亞型具有相似效果,但是在GSK-3和接近的同系物cdc2和erk2間具有明顯區別。CHIR 98014使CHO-IR和鼠肝細胞達到半數大GS刺激反應的濃度分別為106和107 nM。將表達胰島素受體的CHO-IR細胞或原代大鼠肝細胞暴露于遞增濃度的抑制劑CHIR98014中導致GS活性比率高于基礎值的兩倍至三倍的刺激。 |
| 激酶實驗 | 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. |
| 細胞實驗 | 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) |
| 別名 | CHIR98014, CHIR 98014, CT98014 |
| 分子量 | 486.32 |
| 分子式 | C20H17Cl2N9O2 |
| CAS No. | 252935-94-7 |
存儲
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 )
聯系我們：
郵箱：2519696869@qq.com
QQ: 2519696869
電話：18066853083
微信：18066853083
公司介紹：
西安齊岳生物科技有限公司是集化學科研和定制與一體的高科技化學公司。業務范圍包括化學試劑和產品的研發、生產、銷售等。涉及產品為通用試劑的分銷、非通用試劑的定制與研發，涵蓋生物科技、化學品、中間體和化工材料等領域。
主營產品：COF、MOF單體系列：三蝶烯衍生物、金剛烷衍生物、四苯甲烷衍生物、peg、上轉換、石墨烯、光電材料、點擊化學、凝集素、載玻片、蛋白質交聯劑、脂質體、蛋白、多肽、氨基酸、糖化學等。
