产品说明书

TGX-221

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Chemical Structure| 663619-89-4 同义名 : -
CAS号 : 663619-89-4
货号 : A203716
分子式 : C21H24N4O2
纯度 : 99%+
分子量 : 364.441
MDL号 : MFCD11113209
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(32.93 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 3% DMSO+2% Tween80+30% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • p110β

    p110β, IC50:5 nM

  • p110δ

    p110δ, IC50:0.1 μM
描述 Phosphatidylinositol 3-kinases (PI3Ks) are a family of enzymes that catalyse the phosphorylation of phosphatidylinositol at the 3′-position of the inositol ring, producing secondary messenger lipids which control cellular activities including survival, growth and proliferation. These lipid kinases are divided into three distinct classes (Class I, II and III), Class I PI3Ks are heterodimers which consist of one of four closely related catalytic p110 subunits (α, β, δ and γ) and an associated regulatory subunit (p85/p55). TGX-221 is an selective p110β inhibitor, with more than 1000 fold selectivity over the related p110α isoform. TGX-221 can also inhibit the phosphorylation level of its downstream signal. The (R)-enantiomer of TGX-221 (1a) was eventually identified as the bioactive form against the p110β-isoform (IC50 = 6nM and 800nM for the R and S stereoisomers, respectively)[3]. In a vitro study, treatment with 50 - 150 µM TGX-221 for 48h can significantly inhibited the viability of U87 and U251 cells. The IC50 values of TGX-221 in U87 and U251 cells were ~40 and 100 µM, respectively[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
DU145 Growth Inhibition Assay IC50=35.6 ± 0.12 μM 22494444
HUVECs 500 nM Function Assay 1 h reduces Akt phosphorylation 22814170
LNCaP Growth Inhibition Assay IC50=3.98 ± 0.18 μM 22494444
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.74mL

0.55mL

0.27mL

13.72mL

2.74mL

1.37mL

27.44mL

5.49mL

2.74mL
参考文献

[1]Zhao Y, Duan S, et al. Prodrug strategy for PSMA-targeted delivery of TGX-221 to prostate cancer cells. Mol Pharm. 2012 Jun 4;9(6):1705-16.

[2]Straub A, Wendel HP, et al. Selective inhibition of the platelet phosphoinositide 3-kinase p110beta as promising new strategy for platelet protection during extracorporeal circulation. Thromb Haemost. 2008 Mar;99(3):609-15.

[3]Marshall AJ, Lill CL, Chao M, Kolekar SV, Lee WJ, Marshall ES, Baguley BC, Shepherd PR, Denny WA, Flanagan JU, Rewcastle GW. Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: synthesis, biological evaluation and molecular modelling. Bioorg Med Chem. 2015 Jul 1;23(13):3796-808. doi: 10.1016/j.bmc.2015.03.073. Epub 2015 Apr 4. PMID: 25890698.

[4]Yang X, Yang JA, Liu BH, Liao JM, Yuan FE, Tan YQ, Chen QX. TGX-221 inhibits proliferation and induces apoptosis in human glioblastoma cells. Oncol Rep. 2017 Nov;38(5):2836-2842. doi: 10.3892/or.2017.5991. Epub 2017 Sep 22. PMID: 29048665; PMCID: PMC5780035.