Output details

Novel RARa agonists for treatment of neurodegenerative disease

The Corcoran lab obtained a virtual screen and docking of retinoid to the retinoic acid receptor (RAR) alpha. This identified a scaffold of RAR alpha from which further chemistry was carried out to obtain the novel lead compounds exemplified in the patent. The Corcoran lab carried out assays on the compounds to identify EC50 and IC50 of the various compounds (approximately 500 compounds were screened). These structural activity relationships were fed back to the chemists who made further compounds and the assays were reiterated until highly selective compounds were obtained as shown in the patent.

In addition the compounds were tested in the Corcoran lab to delineate drug like properties, including cell survival and their ability to cross the blood brain barrier when given orally.

To show that they were a therapeutic for Alzheimer’s disease eight of the compounds shown in the patent were tested in animal models. Readouts included, Amyloid plaque load (decrease to show the drug working) and behavioural assays (improvement showing the drug working).