Most Pharmacological chaperones (PC’s) described until now are
substrate analogues which bind to the active site of the target protein. C
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 p
tentially offer a much broader therapeutic window. What’s more, such co
pounds are not substrate analogues, thus presenting much better drug-like pro
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.
Pharmacological chaperones, Chemical chaperones
therapy, GM1, Gangliosidosis, Morqui B, Lysosomal Storage Disease,
Lysosomal Storage Disorders
CitacióAymami, J. [et al.]. Enzyme enhancement therapy through non-competitive pharmacological chaperones. A: IWBBIO 2014. "Proceedings IWBBIO 2014". 2014, p. 390-395.