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

National Center For Advancing Translational Sciences

Investigators

Abstract

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.