Phosphatidylinositol 4,5-biphosphate kinases (PIP5Ks) are a family of lipid kinases that phosphorylate phosphatidylinositol 4-phosphate on the D5 position of the inositol ring, thus inducing the production of phosphatidylinositol 4,5-biphosphate (PIP2). PIP5K1α is a lipid kinase that acts on PI3K/AKT/PTEN pathways, and thereby regulates cell survival and migration. ISA-2011B is a PIP5Kα inhibitor with promising anticancer effects. Tumor xenografts established with human prostatic carcinoma cell line 22Rv1 were treated with ISA-2011B(40 mg/kg, 2 weeks) and showed a 3.5-fold smaller tumor volumes compared with those treated with vehicle control (mean volume of tumors were 844.12 mm3 and 243.77 mm3 for vehicle-treated and ISA-2011B-treated groups, respectively)[3]. ISA-2011B treatment at 20 mM or 50 mM diminished AR-V7, CDK1 and PSA expression in PIP5K1α-overexpressing and control 22Rv1 cells, and inhibited AR-V7 and pAKT expression in PC3 cells, respectively[3]. ISA-2011B treatment at 10 µM for 6h or 24h significantly impaired the increases in mRNA levels of IL-6, IL-8, and IL-17A in T lymphocytes from healthy donors which were induced by CD38 stimulation[4]. ISA-2011B at 20 μM dramatically inhibited pSer-473 AKT by 75.55% compared with control in LNCaP cells[5].
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