Small-Molecule Ligands as Potential GDNF Family Receptor Agonists.

ABSTRACT: To find out potential GDNF family receptor α1 (GFRα1) agonists, small molecules were built up by molecular fragments according to the structure-based drug design approach. Molecular docking was used to identify their binding modes to the biological target GFRα1 in GDNF-binding pocket. Thereafter, commercially available compounds based on the best predicted structures were searched from ZINC and MolPort databases (similarity ≥ 80%). Five compounds from the ZINC library were tested in phosphorylation and luciferase assays to study their ability to activate GFRα1-RET. A bidental compound with two carboxyl groups showed the highest activity in molecular modeling and biological studies. However, the relative position of these groups was important. The meta-substituted structure otherwise identi

SUBMITTER: Ivanova L 

PROVIDER: S-EPMC6045390 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature