Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases expressed on the cell membrane that play crucial roles in both developmental and adult cells. Dysregulation of FGFRs has been implicated in a wide variety of cancers, such as urothelial carcinoma, hepatocellular carcinoma, ovarian cancer and lung adenocarcinoma. Due to their functional importance, FGFRs have been considered as promising drug targets for the therapy of various cancers. Multiple small molecule inhibitors targeting this family of kinases have been developed, and some of them are in clinical trials. Furthermore, the pan-FGFR inhibitor erdafitinib (JNJ-42756493) has recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic or unresectable urothelial carcinoma (mUC). This review summarizes the structure of FGFR, especially its kinase domain, and the development of small molecule FGFR inhibitors.

We have developed a novel, silicon-based peptide array for broad biological applications, including potential for development as a real-time point-of-care platform. We employed photolithography on silicon wafers to synthesize microarrays (Intel arrays), containing every possible overlapping peptide within a linear protein sequence covering the N-terminal tail of human histone H2B. Arrays also included peptides with acetylated and methylated lysine residues reflecting post-translational modifications of H2B. We defined minimum binding epitopes for commercial antibodies recognizing modified and unmodified H2B peptides. We further demonstrated that this platform is suitable for highly sensitive methyltransferase and kinase substrate characterization. Intel arrays also revealed specific H2B epitopes recognized by autoantibodies in individuals with systemic lupus erythematosus (SLE) that have increased disease severity. By combining emerging nonfluorescence-based detection methods with an underlying integrated circuit, we are now poised to create a truly transformative proteomics platform with applications in bioscience, drug development, and clinical diagnostics.

Biochemical and structural studies provide information on the mode of action of FGF401 as a selective, reversible covalent inhibitor of FGFR4.

LY2874455 can avoid a steric clash with the mutated gatekeeper residue in FGFR4.

Gastric cancer is the third leading cause of cancer-related mortalities worldwide and mostly incurable. It remains an urgent need for novel strategies in the management of patients with advanced gastric cancer. Chimeric antigen receptor (CAR) T therapy has shown unprecedented clinical success in hematological malignancies and potential utility is going on various solid tumors like gastric cancer. In this study, a broad expression of NKG2D ligands was observed in gastric cancer cell lines, making them suitable targets for gastric cancer therapy. T cells were engineered with an NKG2D-based second-generation CAR and the resulting NKG2D-CAR-T cells showed significantly increased cytolytic activity against gastric cancer compared to untransduced T cells. In vivo, these cells can significantly suppressed the growth of established gastric cancer xenografts. Besides, cisplatin was shown to upregulate NKG2D ligand expression in gastric cancer cells and enhance the susceptibility to NKG2D-CAR-T-cell-mediated cytotoxicity. In conclusion, NKG2D-based CAR-T cells have potent in vivo and in vitro anti-tumor activities against gastric cancer and could be a new paradigm for patients with gastric cancer, either used alone or combined with chemotherapy.

The aim of this paper was to investigate the active components of Schisandra chinensis in the treatment of asthma and the related mechanisms by a network pharmacology approach.

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