Recent research advances in ATX inhibitors: An overview of primary literature.

The autoglobulin gene is the main enzyme for circulating LPA production and has lysophosphatidylcholine D activity, which catalyzes the production of lysophosphatidic acid and choline with lysophosphatidylcholine as substrate. A growing body of experimental evidence suggests that autoglobulin is involved in the pathogenesis of a variety of diseases. This review summarizes the different structural ATX inhibitors classified according to their binding mode to the ATX triple orientation site, and summarizes the conformational relationships and molecular docking of each type with ATX structure, hoping to contribute to the development of novel ATX inhibitors.

Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives as novel EGFRL858R/T790M inhibitors.

EGFR mutations have been identified in 20,000 reported NSCLC (non-small cell lung cancer) samples, and exon 19 deletions and L858R mutations at position 21, known as "classical" mutations, account for 85-90% of the total EGFR (epidermal growth factor receptor) mutations. In this paper, two series of EGFR kinase inhibitors were designed and synthesised. Among them, compound B1 showed an IC50 value of 13 nM for kinase inhibitory activity against EGFRL858R/T790M and more than 76-fold selectivity for EGFRWT. Furthermore, in an in vitro anti-tumour activity test, compound B1 showed an effective anti-proliferation activity against H1975 cells with an IC50 value of 0.087 µΜ. We also verified the mechanism of action of compound B1 as a selective inhibitor of EGFRL858R/T790M by cell migration assay and apoptosis assay.