STAT3-IN-7 is a Sorafenib analogue and potently inhibits the phosphorylation of STAT3. STAT3-IN-7 induces cell apoptosis through SHP-1 dependent STAT3 inactivation. STAT3-IN-7 does not inhibit kinase activity and has anticancer effects.
The signal transducer and activator of transcription 3 (STAT3) is a transcription factor associated with liver injury, inflammation, and regeneration. SC-1 (which is STAT3-IN-7), an aryl sulfonamide azetidine compound, is an orally active STAT3 inhibitor. It is a derivative of the multiple tyrosine kinase inhibitor sorafenib, blocks STAT3 phosphorylation and activation, and induces apoptosis in hepatocellular carcinoma cell lines, and has anticancer activities. SC-1 had dose- and time-dependent effects against cell viability on HSC-T6, LX2, and mouse primary hepatic stellate cells (HSCs). Further, SC-1 down-regulated p-STAT3 and suppressed Mcl-1 and cyclin D1 in both HSC-T6 and LX2 cell lines in a dose-dependent manner. Moreover, SC-1–induced apoptosis was abolished in STAT3-overexpressing HSC cells. In hepatotoxic and cholestatic models, hepatic fibrosis significantly reduced after SC-1 treatment in terms of Metavir fibrosis score and collagen-positive area[2].
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