Drug repositioning for the discovery of therapeutic approaches for pulmonary arterial hypertension

点击翻译按钮获取中文摘要

To develop new drugs for the treatment of pulmonary hypertension (PH) with antiproliferative effects on VSMCs from patients with PAH by drug repositioning of existing drugs, we have chemically synthesized emetine analogs and check antiproliferative activity of the analogs in pulmonary artery smooth muscle cells (PASMCs) from PAH patients (PAH-PASMCs). We have developed 16 analogs of emetine and based on inhibitory effects on PAH-PASMC proliferation, and selected an analog as GMP-emetine for further study in vitro. GMP-emetine showed similar antiproliferative effects on PAH-PASMCs like parent emetine.To identify the specific target protein of GMP-emetine, we have isolated total RNA from PAH-PASMCs after treatment with or without GMP-emetine. Next, we will perform microarray to see the changes of gene expressions in response to GMP-emetine and finally we will identify the specific target protein of GMP-emetine.