AZD 6482

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Chemical Structure| 1173900-33-8 同义名 : KIN-193
CAS号 : 1173900-33-8
货号 : A560000
分子式 : C22H24N4O4
纯度 : 99%+
分子量 : 408.45
MDL号 : MFCD16659062
存储条件：

Pure form Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(122.41 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • p110β

    PI3Kβ, IC50:10 nM

  • p110α

    PI3Kα, IC50:870 nM

  • p110δ

    PI3Kδ, IC50:80 nM
描述 An in vitro kinase assay demonstrates that AZD 6482 (KIN-193) is highly potent in the inhibition of p110β’s kinase activity (IC50 of 0.69 nM) and has 200, 20, and 70-fold selectivity over p110α, p110δ, and p110γ isoforms, respectively. AZD 6482 also exhibits selectivity of ~80 fold over PI3K-C2β and DNA-PK and more than 1,000-fold over other phosphatidylinositol-3 kinase–related kinases (PIKKs). When tumors reach a volume of ~500 mm3, the tumor-bearing mice receives a single IP injection of AZD 6482 (10 mg/kg). The plasma concentration of AZD 6482 is highest at 1 hour post-injection and declined to undetectable levels by 4h. Concentrations of AZD 6482 in both the CA-p110α- and CA-p110β-driven tumors parallel the plasma concentrations. Analyses of tumor lysates harvested at various time points after AZD 6482 injection reveal that the phosphorylation of AKT is significantly reduced at 1hour after AZD 6482 injection in Rat1-CA-p110β tumors, but remain unchanged in Rat1-CAp110α tumors[3]. KIN-193 is efficacious specifically in blocking AKT signaling and tumor growth that are dependent on p110β activation or PTEN loss. Broad profiling across a panel of 422 human tumor cell lines shows that the PTEN mutation status of cancer cells strongly correlates with their response to KIN-193[3]. Further investigation on AZD6482 profile revealed that mutations in RB1, KRAS, NRAS and APC contributed in drug resistance. Changes in both AZD6482-sensitive and -resistant gene sets showed limited impact on prognosis. Western blotting showed AZD6482 did not induce changes in a panel of major downstream effectors of AKT, but substantially increased PMS2 level. AZD6482 also selectively inhibited migration, invasiveness, and colony formation of ccRCC cells with SETD2 mutations[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human 639-V cell Growth inhibition assay Inhibition of human 639-V cell growth in a cell viability assay, IC50=1.63144 μM SANGER
human 786-0 cell Growth inhibition assay Inhibition of human 786-0 cell growth in a cell viability assay, IC50=1.31283 μM SANGER
human A427 cell Growth inhibition assay Inhibition of human A427 cell growth in a cell viability assay, IC50=0.99505 μM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00853450 Antiplatelet Effect Phase 1 Completed - Sweden ... 展开 >> Research Site Lund, Sweden 收起 <<
NCT00688714 Antiplatelet Effect Phase 1 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.45mL

0.49mL

0.24mL

12.24mL

2.45mL

1.22mL

24.48mL

4.90mL

2.45mL
参考文献

[1]Weigelt B, Warne PH, et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3533-44.

[2]Nylander S, Kull B, et al. Human target validation of phosphoinositide 3-kinase (PI3K)β: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kβ inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36.

[3]Jing Ni,et al. Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent. Cancer Discov. 2012 May;2(5):425-33.

[4]Jun Wang,et al. High selectivity of PI3Kβ inhibitors in SETD2-mutated renal clear cell carcinoma. J BUON. Sep-Oct 2015;20(5):1267-75.