Photopharmacology – Reversible photoswitches

The MCS group has developed the first light-regulated mGluR5 negative allosteric modulators

Drugs that target G protein-coupled receptors (GPCRs) account for nearly half of the prescription pharmaceuticals in the market. However, some challenges such as that these drugs are not able to regulate their spatial effects in order to target at a specific organ of interest remain unsolved.

Photopharmacology seeks the precise control of the activity of a drug on receptors or proteins using light and photochemical techniques.

The MCS group has developed the first light-regulated mGluR5 negative allosteric modulators. Administration of these drugs in combination with light irradiation may allow the control and regulation of the activity of the drug locally and in a specific time, by switching between the active and the inactive states in a guided way.

High potency and light control of these compounds has been proved both in vitro, in cultured HEK cells overexpressing mGluR5 and rat cortical astrocytes, showing an IC50 between 30-500 nM and in vivo in a Xenopus tropicalis tadpoles model, by measuring optical control of motility. Due to the roles of mGlu5 receptors in synaptic transmission, these light regulated compounds may have application for pain, Parkinson, epilepsy or anxiety treatments, with local controlled applicatio of a specific target.

This work is developed in collaboration with IBEC (Institute for Bioengineering of Catalonia), Institute of Neuroscience at the Autonomous University of Barcelona (UAB), Faculty of Medicine at University of Barcelona, IGF-CNRS (Montpellier, France) and Sapienza University (Rome, Italy).