SC144 is an orally bioavailable gp130 inhibitor. It 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 when used at a concentration of 20 μM. 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, with IC50 values ranging from 0.4 to 4 μM. It reduces tumor growth in OVCAR-8 and MDA-MB-435 mouse xenograft models.
SC144 is a potent inhibitor of glycoprotein 130 (gp130). SC144 binds to gp130 and blocks STAT3 phosphorylation, nuclear translocation and expression of STAT3 responsive genes. SC144 inhibits the growth of several tumor cell lines, independent of p53 or hormone receptor levels, and inhibits growth of ovarain tumor xenografts in mice.