PI3Kα-IN-4 is a potent, selective, and orally active PI3Kα inhibitor, demonstrating an IC50 of 1.8 nM and exhibiting antitumor activity[1].

PI3Kα:1.8 nM (IC50)

PI3Kα-IN-4 (compound 10) inhibits PI3Kα, β, δ, and γ, with IC50s of 1.8, 271.0, 13.9, and 13.8 nM, respectively in kinase assays[1].PI3Kα-IN-4 inhibits PI3Kα, β, δ, and γ, with IC50s of 12.1,1393, 183, and >10000 nM, respectively in cell based assays[1].

PI3Kα-IN-4 (compound 10) (30 mg/kg; p.o. once daily for 21 d) achieves the best efficacy, which could inhibit tumor growth by 73.0% in mice[1].PI3Kα-IN-4 (15-40 mg/kg; p.o. once daily for 30 d) dose dependently suppresses tumor growth by 62.5% (15 mg/kg), 86.0% (30 mg/kg) and 90.7% (40 mg/kg), respectively in mice[1].PI3Kα-IN-4 (15-40 mg/kg; p.o. once daily; 1-4 h) inhibits the phosphorylation of Akt in a dose- and time-dependent manner in vivo[1].PI3Kα-IN-4 shows high Cmax (mouse 22167, rat 2327 nM) and good bioavailability (mouse 59.4%, rat 46.9%) following oral administration (mouse 10, rat 3 mg/kg)[1].PI3Kα-IN-4 shows t1/2 (mouse 0.99, rat 1.22 h) and low plasma clearance (mouse 4.16, rat 5.28 mL/min/kg) following intravenous injection (mouse 1, rat 1 mg/kg)[1].