TGX-221

FeCl3-induced arterial thrombosis in mice

7-methyl-2-morpholino-9-(1-(phenylamino)ethyl)-4H-pyrido[1, 2-a]pyrimidin-4-one

TGX-221 is a potent, selective PI3K inhibitor for p110beta with IC50 of 8.5 nM.

TGX-221 is dissolved in 10% ethanol, 10% cremaphor, 10% N, N-dimethylacetamine, 70% distilled water.

The activity of TGX-221 against, different isoforms is measured in an in vitro PI3K assay using multiple preparations of recombinant p85/p110. TGX-221 show slow potent to p110delta with IC50 of 211 nM. Furthermore, TGX-221 partially attenuates insulin-induced phosphorylation of Ser473 of PKB in J774.2 macrophage cells. [1] TGX-221 inhibits platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding in an extracorporeal circulation (ECC) model. [2] A recent study shows that after treatment with TGX-221 (0.2, 2, and 20 uM), PC3 cells show, inhibition of proliferation, with a significant reduction of the activity of the p110beta PI3K isoform. [3]

24-72 hours

For measurement of proliferation, cells are seeded in triplicate in 96-well culture plates and incubated overnight to allow cell attachment. The cells are incubated with TGX-221 for 24, 48, and 72 hours. At designated time intervals, cells are quantified by a crystal violet staining-based colorimetric assay. Briefly, cells are fixed by addition of 100 ul of 2.5% glutaraldehyde solution and incubated at room temperature for 30 minutes. Plates are washed three times by submersion in PBS solution. Plates are air-dried and stained by addition of 100 uL of 0.1% solution of crystal violet dissolved in deionized water and incubated for 20 minutes at room temperature, excess dye is removed by extensive washing with deionized water, and plates are air-dried prior to bound dye solubilization in 100 uL of 10% acetic acid. The optical density of dye extracts is measured directly in plates using a microplate reader at 570 nm.

TGX-221 Chemical Structure

, , Dr. Zhang of Tianjin Medical University, TGX-221purchased from Selleck, Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of TGX-221 for 24 hours.

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO