Computer-aided design of multi-target ligands at A₁R, A_2AR and PDE10A, key proteins in neurodegenerative diseases.

ABSTRACT: Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required to produce a clinical effect. In particular, suitable compounds may be useful in treating neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at the adenosine A₁ and A_2A receptors (A₁R and A_2AR) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible ligands that bind to A₁ and A_2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic approach employing in silico target prediction an

SUBMITTER: Kalash L 

PROVIDER: S-EPMC5748027 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature