| 名称 | AZD 6482 |
| 描述 | AZD 6482 (KIN-193) is a potent and selective inhibitor of p110β and PI3Kβ with IC50 values of 0.69nM and 10nM, respectively. AZD 6482 is particularly effective in blocking AKT signaling and tumor growth dependent on p110β activation or PTEN loss. |
| 细胞实验 | For assay of washed platelet aggregation (WPA), the platelet pellets are isolated from human blood and re-suspended to 2 × 1015/L in Tyrodes buffer (TB) containing 1 μM hirudin and 0.02 U/mL apyrase. Then, the platelet suspension is left to rest at room temperature for 30 min. Just prior to time for assay, CaCl2 is added to a final concentration of 2 mM. AZD6482, dissolved in DMSO, is added to a 96-well plate prior to the addition of the washed platelet suspension. The platelet suspension is preincubated with AZD6482 for 5 min. Light absorption at 650 nm is recorded before and after a 5 min plate shake and referred to as recording 0 (R0) and Rl. A mouse anti-human CD9 antibody is added (at a donor specific concentration) to each well prior to next 10 min plate shake and light absorption recording; R2. For data analysis, light absorbance in wells with TB are subtracted from all readings before percent aggregation is calculated according the formula: [(R1-R2)/R1] × 100 = % aggregation. Spontaneous aggregation or pro-aggregatory effect of the inhibitor is evaluated by the same formula, [(R0-Rl)/R0] × 100 = % aggregation. IC50 values are calculated according to the equation, y = {a+[(b-a)/(l+(x/IC50)s)]}, where y = % inhibition; a = 0%; b = 100%; s = the slope of the concentration-response curve; x = AZD6482 concentration. (Only for Reference) |
| 激酶实验 | Assay of PI3K enzyme inhibition: The inhibition of PI3Kβ, PI3Kα, PI3Kγ, and PI3Kδ is evaluated in an AlphaScreen based enzyme activity assay using human recombinant enzymes. The assay measures PI3K-mediated conversion of PIP2 to PIP3. Biotinylated PIP3, a GST-tagged pleckstrin homology (PH) domain and the two AlphaScreen beads form a complex that elicits a signal upon laser excitation at 680 nm. The PIP3 formed in the enzyme reaction competes with the biotinylated PIP3 for binding to the PH domain thus reducing the signal with increasing enzyme product. The AZD6482 is dissolved in DMSO and added to 384 well plates. PBKβ, PBKα, PBKγ, or PBKδ is added in a Tris buffer (50 mM Tris pH 7.6, 0.05% CHAPS, 5 mM DTT, and 24 mM MgCl2) and allowed to preincubate with AZD6482 for 20 minutes prior to the addition of substrate solution containing PIP2 and ATP. The enzyme reaction is stopped after 20 minutes by addition of stop solution containing EDTA and biotin-PIP3, followed by addition of detection solution containing GST-grpl PH and AlphaScreen beads. Plates are left for a minimum of 5 hours in the dark prior to analysis. The final concentration of DMSO, ATP and PIP2 in the assay are, 0.8%, 4 μM, and 40 μM, respectively. IC50 values are calculated according to the equation, y = {a+[(b-a)/(l+(x/IC50)s)]}, where y = % inhibition; a = 0%; b = 100%; s = the slope of the concentration-response curve; x = AZD6482 concentration. |
| 体外活性 | 方法：AZD 6482 (KIN-193) （0.625，1.25，2.5，5，10，20 ， 40 μM，48小时）测定处理 U87 和 U118细胞，CCK8测定其对 U87 和 U118 细胞增殖的抑制作用。
结果：AZD 6482以剂量依赖式方式抑制两种细胞系的活力，其中U118 细胞比 U87 细胞更敏感，IC50值分别为 7.989 和 9.061μM。[4] |
| 体内活性 | 方法：AZD 6482 (KIN-193) （20 mg/kg，腹腔注射，每天两次）或 GDC-0941（150 mg/kg，口服，每天一次）处理 HCC70、PC3 和 HCC1954 的异种移植肿瘤小鼠，研究KIN-193 对 PTEN 缺陷肿瘤的体内效应。
结果：AZD 6482 显著抑制 HCC70 和 PC3 肿瘤的肿瘤生长，但未能阻断 HCC1954 肿瘤的生长。[2] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.9 mM), Sonication is recommended.
DMSO : 45 mg/mL (110.17 mM), Sonication is recommended.
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| 关键字 | PI3Kδ | PI3Kγ | PI3Kβ | PI3Kα | PI3K | Phosphoinositide 3-kinase | KIN-193 | KIN193 | Inhibitor | inhibit | DNA-PK | DNAPK | AZD-6482 | AZD 6482 | Autophagy |
| 相关产品 | Naringin | Guanidine hydrochloride | Gefitinib | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Sodium butanoate | Hyaluronic acid | Hydroxychloroquine | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
| 相关库 | 抑制剂库 | 经典已知活性库 | 已知活性化合物库 | 代谢化合物库 | 激酶抑制剂库 | 抗衰老化合物库 | 癌细胞分化化合物库 | 抗肥胖化合物库 | 免疫/炎症分子化合物库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |