生物活性

• 靶点

  Akt1 IC50:180nM

  Akt2 IC50:328nM

  Akt3 IC50:38nM

• 描述AKT is the central node of the PI3K/AKT/ mTOR pathway. The PH domain and ATP-competitive site are the main target site for research of new compound^[2]. GSK2141795 is an ATP-competitive pan AKT inhibitor with Ki values of 180, 328 and 38nM for AKT 1, 2 and 3 (determined by the kinobead competition binding assay)^[1]. Treatment of GSK2141795 on concentration of 1-10 μM can induce G1-arrest and decrease the phosphorylation level of multiple AKT substrate including PRAS40, FOXO and Caspase 9 in BT474 and LNCaP cell lines in a concentration-dependent manner, accompanied by feedback increase in AKT phosphorylation. In cell growth inhibition study, overall 81% of the hematological cell lines were sensitive to GSK2141795 (EC50 <1 uM). Among solid tumor cell lines, 36% had EC50<1 μM in response to GSK2141795. Cell lines containing activating mutations to KRAS, NRAS or BRAF showed more resistence to GSK2141795. Mice bearing SKOV3 ovarian tumor xenografts orally treated with 10, 20 and 30 mg/kg GSK2141795, once daily for 21 days, displayed a 73, 85 or 93% TGI, respectively^[3]. Several clinical trials of GSK2141795, including a phase 1 study of GSK2141795 of treatment for solid tumors, have been completed (see in https://clinicaltrials.gov/).
• 作用机制GSK2141795 is an ATP-competitive AKT inhibitor.