Identification and use of shp2 conformational disruptors for cancer treatment

Abstract

Compounds were identified from SHP2 Protein Conformational Array (PCA) ELISA. These compounds can disrupt SHP2 Higher Order Structure (HOS) in vitro and induce SHP2 degradation in multiple cancer cell lines. The SHP2-KRAS-ERK pathway analysis indicated that these identified compounds could induce inactivation of the active form of ERK, P-ERK. In addition, some of the compounds can induce SHP2 and/or KRAS degradation in multiple cancer cell lines. Cancer cell line testing demonstrated that these compounds identified through SHP2 HOS disruption showed dose-dependent growth inhibition. Since the SHP2-KRAS-ERK pathway plays an important role in cancer development, these compounds can be used as potential cancer treatments.

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