STAT3 inhibitor LY5 is a specfic STAT3 small molecule inhibitor, binds to STAT3 SH2 domain wioth Kd of 2.5 uM.
LY5 (0.5-1 uM, 8 h) inhibits constitutive STAT3 phosphorylation in Ewing's sarcoma cell line EW8.
LY5 (0.25-1 uM) inhibits IL-6 induced STAT3 phosphorylation in MCF-7 cells, but not STAT1 phosphorylation induced by IFN-γ.
LY5 induces apoptosis in human sarcoma cells (RD2, RH30,and U2OS) with IC50 of 0.5-1.4 uM.
LY5 (5 mg/kg, IP) suppresses tumor growth of MDA-MB-231 breast cancer cells in mouse tumor model in vivo.
LY5 down-regulates the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21, in human medulloblastoma cells.
LY5 inhibits the induction of STAT3 phosphorylation by IL-6, IGF-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but does not inhibit STAT1 and STAT5 phosphorylation stimulated by IFN-γ and EGF, respectively.
LY5 blocks the STAT3 nuclear localization induced by IL-6, but does not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively.