ISA-2011B is an inhibitor of PIP5K1α. It also has promising anticancer effects.

ISA-2011B significantly decreases AR-V7 and CDK1 levels in both the nucleus and cytoplasm of 22Rv1 cells, demonstrating strong binding affinity towards PIP5K1α and both MARK1 and MARK4 among 460 kinases. In PC-3 cells, ISA-2011B treatment reduces PIP5K1α expression by 78.6%[1] and eliminates nuclear AR expression without affecting cytoplasmic AR[2]. Additionally, ISA-2011B markedly lowers the proliferation rates of PC-3 cells to 58.77%, 48.65%, and 21.62% at doses of 10, 20, and 50 μM, respectively, compared to controls.

Overexpression of AR-V7 enhances PIP5K1α levels, accelerating prostate cancer (PCa) growth in xenograft mice. Conversely, the PIP5K1α inhibitor ISA-2011B significantly curtails the proliferation and invasiveness of AR-V7 overexpressing xenograft tumors. ISA-2011B effectively impedes tumor cell growth in xenograft mice by targeting the PIP5K1α-related PI3K/AKT pathways, including those responsible for survival, proliferation, and invasion[1]. Furthermore, ISA-2011B interferes with AR-V7 protein stabilization through its dependency on PIP5K1α, thereby hindering the aggressive growth of AR-V7-high tumors in xenograft models[2].