Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity

Design and discovery of new classes of anticancer agents with unique mechanisms ofaction is an urgent medical need. During the past several years, a series of salicylhydrazide class ofcompounds were reported to possess remarkable potency in a large panel of cancer cell lines fromdifferent tumor origins. In particular, the optimized lead compound, SC144, was further investigatedand selected as a valuable drug candidate endowed with favorable pharmacokinetic and antiproliferativeproperties in various in vitro and in vivo xenograft models. This lead compound is activein cells resistant to conventional chemotherapies, synergistic with several standard-of-care drugs, and possesses an uniquemechanism acting through the inhibition of the gp130-STAT3-survivin axis. Because of this novel mechanism, clinicaldevelopment of SC144 will provide new therapeutic options for diverse cancers.