产品说明书

Taselisib

Print
Chemical Structure| 1282512-48-4 同义名 : GDC-0032;RG-7604;GDC0032, GDC0032, GDC 0032, RG7604, RG7604, RG 7604, Taselisib;​Taselisib
CAS号 : 1282512-48-4
货号 : A139829
分子式 : C24H28N8O2
纯度 : 99%+
分子量 : 460.531
MDL号 : MFCD28167893
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(54.29 mM)，配合低频超声，并水浴加热至45℃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 4 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • p110γ

    PI3Kγ, Ki:0.97 nM

  • p110β

    PI3Kβ, Ki:9.1 nM

  • C2β

    C2β, IC50:292 nM

  • p110α

    PI3Kα, Ki:0.29 nM
描述 Phosphoinositide-3 kinase (PI3K) plays important role in response to various extracellular triggers and in activation of downstream Akt and mTOR, which together control the tumor cell proliferation. GDC-0032 is the inhibitor of PI3K with Ki of 0.29 nM for PI3Kα, with IC50 values of 4.0 nM and 25 nM for p-Akt and MCF7-neo/HER2 cell lines respectively. In MCF7-neo/Her2 xenograft model, treatment of GDC-0032 with concentrations ranging from 1.4 to 22.5 mg/kg resulted in an increasing of tumor growth inhibition with corresponding inhibition rates from 19% to 123%, dose-dependently. Akt phosphorylation was also decreased by 59% when treated with 2.8 mg/kg of GDC-0032. In a panel containing 235 kinases, treated them with 1 μM GDC-0032 led to >70% inhibition in PI3K-C2 beta, PI3Kα, PI3Kδ, PI3Kγ and hVPS34. The IC50 values for PI3K-C2 beta and hVPS34 were 292 nM and 374 nM, respectively[1]. In a panel of 26 HNSCC cell lines, GDC-0032 showed gradient inhibition IC50 values ranging from 0.05 to 2 μM. The 4 cell lines with IC50 values 2 μM are most resistant to GDC-0032 due to the mutation or loss of PTEN gene. In Cal-33 cells harboring a PIK3CA H1047R mutation, treatment of GDC-0032 with concentrations ranging from 0 to 4 μM prevented AKT phosphorylation and inhibited S6 kinase level, leading to an induction of apoptosis. However, less effect on AKT/mTOR signaling in cell lines containing PTEN mutations was also observed, which means that GDC-0032 only inhibits PI3Kα-dependent signaling. Also in Cal-33 cells, the combination treatment of GDC-0032 and radiation led to more apoptotic, more non-apoptotic cell death and slower cell growth rates. In Cal-33 xenografts mice model with 5 mg/kg of GDC-0032, AKT and PRAS40 phosphorylation were almost completely abrogated as well as the decreasing of 4EBP-1 and S6 phosphorylation at 2 hours treatment. The treatment also mildly improved the proportion of cells in G1 phase and decreased G2 phase of the cell cycle over 72 hours[2].
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 MOLM16 cells Proliferation assay 72 h Antiproliferative activity against human MOLM16 cells after 72 hrs by Cell Titer-Blue assay 22727640
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.86mL

2.17mL

1.09mL

21.71mL

4.34mL

2.17mL
参考文献

[1]Ndubaku CO, Heffron TP, et al. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013;56(11):4597-610.

[2]Zumsteg ZS, Morse N, et al. Taselisib (GDC-0032), a Potent β-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations. Clin Cancer Res. 2016;22(8):2009-19.