Discovery of novel substituted pyridine carboxamide derivatives as potent allosteric SHP2 inhibitors.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2), a critical regulator of proliferation pathways and immune checkpoint signaling in various cancers, is an attractive target for cancer therapy. Here, we report the discovery of a novel series of substituted pyridine carboxamide derivatives as potent allosteric SHP2 inhibitors. Among them, compound C6 showed excellent inhibitory activity against SHP2 and antiproliferative effect on MV-4-11 cell line with IC values of 0.

Design, synthesis, and evaluation of 4(1H)-quinolinone and urea derivatives as KRAS inhibitors with potent antitumor activity against KRAS-mutant non-small cell lung cancer.

KRAS is the most prevalent KRAS mutation in non-small cell lung cancer (NSCLC) and has emerged as a promising therapeutic target. Herein, two series of novel 4(1H)-quinolinone and urea compounds were designed based on the reported KRAS inhibitor SH-9. Many compounds showed significantly growth inhibitory activity against human NSCLC cells with KRAS mutation in cell viability assays.