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ISA-2011B

CAS No. : 1395347-24-6

產(chǎn)品活性：ISA-2011B is a PIP5K1α inhibitor with promising anticancer effects .

研究領(lǐng)域：Others

作用靶點(diǎn)：Others

In Vitro: The 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.

In Vivo: ISA-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.

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