Ack1 inhibitor 1 is a potent and selective orally active inhibitor of ACK1 kinase, with an IC50 value of 2.1 nM. It effectively inhibits the phosphorylation of ACK1 and the activation of downstream AKT, demonstrating anti-tumor activity [1].

Ack1 inhibitor 1 (Compound 10zi) demonstrates inhibitory effects in 67R and H1975 cell lines with IC50 values of 3.71 μM and 4.18 μM, respectively [1]. When used alone or in combination with ASK120067 (0 nM-5000 nM, 72 h), Ack1 inhibitor 1 enhances the antitumor activity in 67R cells [1]. Furthermore, a dose-dependent inhibition of phosphorylation of ACK1 and AKT is observed in 67R cells treated with Ack1 inhibitor 1 at concentrations of 1 μM and 5 μM over 6 h [1]. Cell viability assays [1] in the 67R cell line, a derivative of the H1975 cells resistant to ASK120067, showed a pronounced synergistic anti-growth effect when used in conjunction with ASK120067, achieving a synergy score of 10.83. Protein blot analysis [1] in 67R cells at 1 μM and 5 μM for 6 h, with or without EGF stimulation for 30 minutes, revealed moderate reduction in p-ACK1 and p-AKT at 1 μM and more significant suppression of p-AKT at 5 μM, although complete inhibition of p-ACK1 was not achieved.

When administered orally at a single dose of 10 mg/kg in SD rats, Ack1 inhibitor 1 (Compound 10zi) achieves an AUC of 1920.56 h•ng/mL, a C_max of 119.52 μg/L, and a bioavailability rate of 19.80%.