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Capivasertib

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Chemical Structure| 1143532-39-1 同义名 : AZD5363
CAS号 : 1143532-39-1
货号 : A260907
分子式 : C21H25ClN6O2
纯度 : 99%+
分子量 : 428.915
MDL号 : MFCD22628785
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(279.78 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：

IP 2% DMSO+2% Tween80+40% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • Akt3

    Akt3, IC50:8 nM

  • Akt1

    Akt1, IC50:3 nM

  • Akt2

    Akt2, IC50:8 nM
描述 AKT is the central node of PI3K/AKT/mTOR pathway. The PH domain and ATP-competitive site are the main target site for research of new compound[1]. AK316078 is an ATP-competitive pan AKT inhibitor with IC50 values of 13, 66, 57 nM for AKT 1, 2 and 3 (measured by enzyme assays), respectively[2]. AZD5363 on concentration of 0.3 – 10 μM effectively inhibited phosphorylation of S6 and 4E-BP1, which are the downstream of AKT, in LNCaP and BT474 cells, whereas it increased phosphorylation of AKT at both Ser473 and Thr308 like other ATP-competitive AKT inhibitors. Treatment with 3 μM AZD5363 for 2h can induce FOXO3a nuclear translocation. In cell growth inhibition assays, HER2+ and ER+ breast cancer cell lines showed most consistently sensitivity to AZD5363 (<3 μM). Oral administration of AZD5363 at 100 mg/kg twice daily resulted in 80% inhibition in HER2+ amplified, PIK3CA mutant BT474c xenografts. AZD5363 at 150 mg/kg twice daily caused pronounced tumor regression (129% inhibition), whereas 75 mg/kg twice daily resulted in 111% inhibition in HER2+ amplified, PIK3CA mutant HCC-1954 breast cancer xenograft[3]. Several clinical trials of AZD5363, including a completed phase 2 study of treatment for invasive breast cancer, have been done (see in https://clinicaltrials.gov/).
作用机制 AZD5363 is an ATP-competitive AKT inhibitor.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
1%MCF7 400 nM Growth Inhibition Assay 6 d increased drug sensitivity of 4-OHT and fulvestrant 26351323
23132/87 Growth Inhibition Assay IC50=1.671 μM 24088382
AGS Growth Inhibition Assay IC50=0.552 μM 24088382
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.66mL

2.33mL

1.17mL

23.31mL

4.66mL

2.33mL
参考文献

[1]Huck BR, Mochalkin I, et al. Recent progress towards clinically relevant ATP-competitive Akt inhibitors. Bioorg Med Chem Lett. 2017 Jul 1;27(13):2838-2848.

[2]Addie M, Ballard P, et al. Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases. J Med Chem. 2013 Mar 14;56(5):2059-73.

[3]Davies BR, Greenwood H, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012 Apr;11(4):873-87.

[4]Searle EJ, Telfer BA, et al. Akt inhibition improves long-term tumour control following radiotherapy by altering the microenvironment. EMBO Mol Med. 2017 Dec;9(12):1646-1659.