Pharmacological chaperones are small molecule synthetic compounds that induce the “correct” folding by binding to the protein and/or increase the target protein trafficking to cellular destination. Ultimately, pharmacological chaperones increase the cellular activity of the enzyme.
The first-generation pharmacological chaperones were competitive inhibitors of mutant enzymes. Allosteric chaperones are non-inhibitory ligands, targeting previously unknown binding pockets, limit the risk of adverse enzymatic inhibition. In ATLAS, the Chassys Platform is specially designed for the discovery and development of second-generation allosteric pharmacological chaperones.
Drug repurposing is meaningful in the context of rare and ultrarare diseases. Consequently, pharmacological chaperones developed in ATLAS embrace new chemical entities and repurposed drugs.