The AKT/PKB pathway plays a central role in
tumor development and progression and is often up-regulated in different
tumor types, including
melanomas. We have recently reported on the in silico approach to identify putative inhibitors for AKT/PKB. Of the reported hits, we selected
BI-69A11, a compound which was shown to inhibit AKT activity in in vitro
kinase assays. Analysis of
BI-69A11 was performed in
melanoma cells, a
tumor type that commonly exhibits up-regulation of AKT. Treatment of the UACC903 human
melanoma cells, harboring the PTEN mutation, with
BI-69A11 caused efficient inhibition of AKT S473 phosphorylation with concomitant inhibition of AKT phosphorylation of PRAS40. Treatment of
melanoma cells with
BI-69A11 also reduced AKT
protein expression, which coincided with inhibition of AKT association with HSP-90.
BI-69A11 treatment not only caused cell death of
melanoma, but also prostate tumor cell lines. Notably, the effect of
BI-69A11 on cell death was more pronounced in cells that express an active form of AKT. Significantly, intra-peritoneal injection of
BI-69A11 caused effective regression of
melanoma tumor xenografts, which coincided with elevated levels of cell death. These findings identify
BI-69A11 as a potent inhibitor of AKT that is capable of eliciting effective regression of xenograft
melanoma tumors.