Enzyme Enhancement Therapy through non-competitive pharmacological chaperones

Most Pharmacological chaperones (PC's) described until now are substrate analogues which bind to the active site of the target protein. Conse- quently, such PC's also inhibit the target protein at higher concentrations thus rendering a narrow therapeutic window and have poor drug-like properties. Through our proprietary technology platform SEE-Tx™, we identify a new generation of non-substrate competitive pharmacological chaperones which po- tentially offer a much broader therapeutic window. What's more, such com- pounds are not substrate analogues, thus presenting much better drug-like prop- erties, particularly for indications with CNS involvement. Here we present our methodology to identify non-competitive pharmacological chaperones applied to the enzyme beta-galactosidase, whose deficiency is related with GM1 Gangliosidosis and Morquio B.