SC144 (SC-144) is the first-in-class orally active small-molecule gp130 inhibitor with a broad-spectrum anticancer activity.
SC144 (20 uM) inhibits phosphorylation of STAT1, STAT3, and Akt induced by leukemia inhibitory factor (LIF) and IL-6, but not IFN-γ, in OVCAR-8 ovarian cancer cells.
SC144 binds gp130, induces gp130 phosphorylation (S782) and deglycosylation, abrogates Stat3 phosphorylation and nuclear translocation, and further inhibits the expression of downstream target genes.
SC144 induces cell cycle arrest at the G0/G1 phase in MDA-MB-435 breast and HT-29 colorectal cancer cells and inhibits proliferation of 14 cancer cell lines, including prostate, ovarian, lung, breast, and colorectal cancer cells (IC50=0.4-4 uM).
SC144 reduces tumor growth in OVCAR-8 and MDA-MB-435 mouse xenograft models.
