Midkine inhibitors: application of a simple assay procedure to screening of inhibitory compounds

<p>Abstract</p> <p>Background</p> <p>Midkine is a heparin-binding cytokine and is involved in etiology of various diseases. Thus, midkine inhibitors are expected to be helpful in treatment of many diseases.</p> <p>Methods</p> <p>We developed a simple assay for midkine activity based on midkine-dependent migration of osteblastic cells. Midkine inhibitors were searched as materials that inhibit this midkine activity. To develop peptides that inhibit midkine activity, we constructed models in which C-terminal half of midkine interacted with α₄β₁-integrin. Low molecular weight compounds which are expected to bind to midkine with high affinity were searched by <it>in silico </it>screening with the aid of Presto-X2 program.</p> <p>Results</p> <p>Among peptides in putative binding sites of midkine and the integrin, a peptide derived from β₁-integrin and that derived from the first β sheet of the C-terminal half of midkine significantly inhibited midkine activity. Two low molecular weight compounds found by <it>in silico </it>screening exhibited no toxicity to target cells, but inhibited midkine activity. They are trifluoro compounds: one (PubChem 4603792) is 2-(2,6-dimethylpiperidin-1-yl)-4-thiophen-2-yl-6-(trifluoromethy)pyrimidine, and the other has a related structure.</p> <p>Conclusions</p> <p>The assay procedure is helpful in screening midkine inhibitors. All reagents described here might become mother material to develop clinically effective midkine inhibitors.</p

Review of swimming fully clothed program : one of our draft plans for revision of the maritime practice at the Tokyo University of Fisheries III

東京水産大学 食品生産学科東京水産大学 海洋生産学科東京水産大学 海洋生産学科東京水産大学 海洋生産学科東京水産大学 研究練習船東京水産大学 海洋環境学科東京水産大学 資源管理学科東京水産大学 資源育成学

Application of swimming fully clothed to novices : one of our draft plans for revision of the maritime practice at the Tokyo University of Fisheries - II

東京水産大学食品生産学科東京水産大学海洋生産学科東京水産大学海洋生産学科東京水産大学海洋生産学科東京水産大学研究練習船東京水産大学海洋環境学科東京水産大学資源管理学科東京水産大学資源育成学