A drug based approach for integrin-mediated alleviation for muscular dystrophy

该项目目前的目标是对活性先导分子舒尼替尼进行化学修饰，目的是降低分子的抗增殖活性，同时保持其对7整合素基因表达产生的激动剂活性。舒尼替尼是一种受体酪氨酸激酶抑制剂小分子，被批准用于肾细胞癌和胃肠道间质瘤。舒尼替尼是与NCATS鉴定的原HTS击中分子SU9516属于同一支架家族的分子。

The current goal of the project is the chemical modification of the active lead molecule Sunitinib, with the aim of reducing the molecules anti-proliferative activity, while mantaining its agonist activity towards the production of 7 integrin gene expression. Sunitinib is a receptor tyrosine kinase inhibitor small molecule, approved for use in both renal cell carcinoma and gastrointestinal stromal tumors. Sunitinib is a molecule belonging to the same scaffold family as the original HTS hit molecule identified by NCATS, SU9516. During this period, docking and modeling studies were performed to select the most adequate place in the scaffold of the lead molecule to perform modifications. Several molecules were synthesized to test the hypothesis of the modelling/computational studies regarding the selective activity towards the production of integrin, while reducing the anti-proliferative activity. The synthesized molecules are awaiting testing.