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

为了通过药物重新定位，开发对PAH患者VSMCs具有抗增殖作用的治疗肺动脉高压（PH）的新药，我们化学合成了艾美汀类似物，并检测了类似物对PAH患者肺动脉平滑肌细胞（PAH-PASMCs）的抗增殖活性。我们开发了16种艾美汀类似物，基于对PAH-PASMC增殖的抑制作用，选择了一种类似物作为gmp -艾美汀进行体外进一步研究。gmp -艾美汀对PAH-PASMCs的抗增殖作用与母体艾美汀相似。为了鉴定GMP-emetine的特异性靶蛋白，我们从加或不加GMP-emetine治疗的PAH-PASMCs中分离出总RNA。接下来，我们将通过微阵列观察基因表达对GMP-emetine的响应变化，最后我们将确定GMP-emetine的特异性靶蛋白。

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.