| Description | TG100-115 is a PI3Kγ/δ inhibitor (IC50: 83/235 nM), with fewer effects on PI3Kα/β. |
| In vitro | 在患心肌梗塞的啮齿目动物和猪模型中,TG100-115（0.5-5 mg/kg）具有有效的心脏保护功能,阻止梗塞恶化,保存心机功能.在Miles实验模型中,TG100-115（1-5 mg/kg）使大鼠的水肿和炎症降低.TG100-115（5 mg/kg）可使小鼠体内Sema3A或血管内皮生长因子相关的血管通透性显著降低,表明这两种因子对血管通透性的诱导作用可能依赖于PI3Kγ/δ.在患哮喘鼠模型,TG100-115可使肺嗜酸性粒细胞增多症显著减弱,并使白细胞介素13和粘蛋白积累受到抑制. |
| In vivo | 在人脐静脉内皮细胞中,TG100-115（10 μM）不影响细胞增殖和VEGF刺激的ERK磷酸化,但会阻断其他血管内皮生长因子信号通路, 如VE-钙粘蛋白磷酸化,从而抑制血管内皮生长因子诱导的VE钙粘蛋白整体水平提高。 TG100-115（0.125-10 μM）对FGF刺激的Akt磷酸化也有抑制作用。TG100-115对PI3Kα/β的抑制效果很弱（IC50：1.2/1.3 mM）。TG100-115对血管内皮生长因子调节的p70S6和mTOR激酶磷酸化有抑制作用。 |
| Cell experiments | Cells plated in 96-well cluster plates (5 × 103 cells/well) are cultured in assay medium (containing 0.5% serum and 50 ng/ml VEGF) in the presence or absence of TG100-115, and cell numbers are quantified by XTT assay 24, 48, or 72 hours late(Only for Reference) |
| Target activity | PI3Kγ:83 nM |
| molecular weight | 346.34 |
| Molecular formula | C18H14N6O2 |
| CAS | 677297-51-7 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) DMSO: 40 mg/mL (115.49 mM) Ethanol: < 1 mg/mL (insoluble or slightly soluble) |
| References | 1. Doukas J, et al. Proc Natl Acad Sci U S A, 2006, 103(52), 19866-119871. 2. Palanki MS, et al. J Med Chem, 2007, 50(18), 4279-4294. 3. Acevedo LM, et al. Blood, 2008, 111(5), 2674-2680. 4. Doukas J, et al. J Pharmacol Exp Ther, 2009, 328(3), 758-765. |