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Oncogene ; 35(20): 2675-80, 2016 05 19.
Article in English | MEDLINE | ID: mdl-26119932

ABSTRACT

It is well known that specific signal transduction inhibitors rarely suffice as anti-cancer agents. In most cases, tumors possess primary drug resistance due to their inherent heterogeneity, or acquire drug resistance due to genomic instability and acquisition of mutations. Here we expand our previous study of the novel compound, NT157, and show that it acts as a dual-targeting agent that invokes the blockage of two signal transduction pathways that are central to the development and maintenance of multiple human cancers. We show that NT157 targets not only IGF1R-IRS1/2, as previously reported, but also the Stat3 signaling pathway and demonstrates remarkable anti-cancer characteristics in A375 human melanoma cells and in a metastatic melanoma model in mice.


Subject(s)
Antineoplastic Agents/pharmacology , Melanoma/drug therapy , Molecular Targeted Therapy/methods , Pyrogallol/analogs & derivatives , Receptors, Somatomedin/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Sulfonamides/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Drug Discovery , Humans , Melanoma/pathology , Neoplasm Invasiveness , Pyrogallol/pharmacology , Pyrogallol/therapeutic use , Receptor, IGF Type 1 , Sulfonamides/therapeutic use
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