Study of the plasticity of the Glucocorticoid Receptor using selective modulators.

01 January 2018 → Ongoing
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Glucocorticoid Receptor
Project description

Everybody probably knows someone who uses or has used glucocorticoids ("cortisone") as
therapy, since they represent one of the most frequently prescribed classes of drugs. Therefore,
most people know about the side effects, with the ‘moon face’ as one of the most visible and
characteristic ones. Glucocorticoids are used to treat inflammatory diseases and certain types of
cancer. Many research groups are focusing on the development of molecules with the same
desired anti-inflammatory properties as the currently available drugs, but which induce less side
effects. Both the classic drugs and novel drug candidates induce their effects via binding the same
cellular receptor, the glucocorticoid receptor. This binding occurs via a so-to-speak ‘lock and key’
mechanism. Unfortunately, only a part of the shape (3D structure) of this receptor (the ‘lock’) is
known, which makes it hard to find the best ‘keys’. Therefore, it is important to know more about
the 3D structure of this receptor inside cells and also investigate how different keys can change
the shape of the lock upon binding. We believe that if we link a certain 3D shape of the receptor to
strong anti-inflammatory properties with reduction of side effects, finding better ligands could be
made much easier, since we could then select for molecules that ‘fit’ best in this ‘desired’ 3D
shape of the receptor.