Description
ISA-2011B is a PIP5K1α inhibitor with promising anticancer effects. In VitroThe proliferation rate of PC-3 cells after treatment with ISA-2011B at 10, 20, and 50 µM is significantly reduced to 58.77%, 48.65%, and 21.62% of vehicle-treated controls, respectively. ISA-2011B exhibits the highest binding affinity to PIP5K1α, and to MAP/microtubule affinity-regulating kinase 1 and 4 (MARK1 and MARK4) across 460 kinases. ISA-2011B treatment inhibits PIP5K1α expression by 78.6% in PC-3 cells. ISA-2011B leads to a remarkable reduction in AR-V7 and CDK1 in both nucleus and cytoplasm of 22Rv1 cells. ISA-2011B treatment also abolishes AR expression in the nucleus, without depleting the cytoplasmic AR. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell AssayCells are grown in phenol red-free RPMI-1640 medium 24 hours and then are treated with drugs alone or in combination for 24 hours or 48 hours. MDV3100 at 5 µM or ISA-2011B at 20 µM or 50 µM final concentrations or solvent DMSO 1% is used. For treatment of 22Rv1 cells with MG132, a proteasome inhibitor, cells are treated with MG132 at 1 µM. For combination treatment of MG132 and ISA-2011B, cells are pre-treated with MG132 for 30 min at 1 µM prior to treatment of ISA-2011B. MCE has not independently confirmed the accuracy of these methods. They are for reference only