中文同义词:
PIP5KΑ抑制剂(ISA-2011B)
英文同义词:
ISA2011B; ISA 2011B;ISA-2011B;5H-1,3-Dioxolo[4,5-g]pyrazino[1,2-b]isoquinoline-7,10-dione, 5-(5-chloro-1H-indol-3-yl)-8,9,10a,11-tetrahydro-9-methyl-, (5S,10aS)-
生物活性
ISA-2011B是PIP5K1α的抑制剂， 具有抗癌活性。
体外研究
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.
体内研究
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.
