3CAI 是特异性的AKT1和AKT2抑制剂。

3CAI is a potent and specific AKT1 and AKT2 inhibitor which showed significant inhibition of AKT in an in vitro kinase assay and suppressed expression of AKT direct downstream targets such as mTOR and GSK3β as well as induced growth inhibition and apoptosis in colon cancer cells.

3CAI is a potential inhibitor of AKT and is a much more potent AKT1 inhibitor than PI3K (60% inhibition at 1 vs 10 μM, respectively). HCT116 and HT29 colon cancer cells are seeded on 6 cm dishes in 1% FBS/McCoy's 5A (HCT116) with 3CAI (4 μM), I3C or the AKT inhibitor and then incubated for 4 days. Results show that the number of apoptotic cells is significantly increased by 3CAI in HCT116 and HT29 colon cancer cells compared with untreated control cells[1]. AKT-mediated phosphorlyation site of mTOR (Ser2448) and GSK3β (Ser9) are substantially decreased by 3CAI in a time-dependent manner. Moreover, pro-apoptotic marker proteins p53 and p21 are also upregulated by 3CAI after 12 or 24 h of treatment. The effect of 3CAI on the kinase activities of AKT1, MEK1, JNK1, ERK1 and TOPK is tested using in vitro kinase assays based on these screening data. The results show that 3CAI (1 μM) suppresses only AKT1 kinase activity and the other kinases tested are not affected by 3CAI. 3CAI substantially suppresses AKT1 activity as well as AKT2 activity in a dose dependent manner. 3CAI inhibits down-stream targets of AKT and induces apoptosis.

HCT116 cancer cells are injected into the right flank of individual athymic nude mice. Mice are orally administered 3CAI at 20 or 30 mg/kg, I3C at 100 mg/kg, or vehicle 5 times a week for 21 days, to examine the antitumor activity of 3CAI in vivo. Expression of these AKT-target proteins is strongly suppressed by 30 mg/kg of 3CAI in tumor tissues[1]. Treatment of mice with 30 mg/kg of 3CAI significantly suppresses HCT116 tumor growth by 50% relative to the vehicle-treated group (p<0.05). Remarkably, mice seem to tolerate treatment with these doses of 3CAI without overt signs of toxicity or significant loss of body weight compared with vehicle-treated group.

28755-03-5

C10H8ClNO

193.63

DMSO:246 mg/mL (1270.46 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years