Lajarín-Cuesta Rocío, Arribas Raquel L, De Los Ríos Cristóbal
a Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina , Universidad Autónoma de Madrid , Madrid , Spain.
b Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica , Hospital Universitario de la Princesa , Madrid , Spain.
Expert Opin Ther Pat. 2016;26(3):389-407. doi: 10.1517/13543776.2016.1135903. Epub 2016 Feb 7.
The role played by phosphoprotein phosphatases (PPP) enzymes makes them of interest as therapeutic targets to treat pathologies including neurodegenerative diseases, cancer and autoimmune diseases, but also liable to cause severe side effects. This fact has hindered the study of PPP ligands as potential drugs. Fortunately, recent advances in the comprehension of PPP biochemistry have given rise to the development of refined pharmacological strategies to selectively target phosphatases and limit the possible generation of adverse reactions.
This review summarizes the most relevant patents claiming the use of PPP ligands to treat human diseases in the last decade (2005-2015). It also includes some pharmacological strategies aiming to indirectly modulate PPP functionality by interacting with PPP-regulating enzymes.
There is still much work to be done to validate PPP enzymes as eligible targets for the development of new drugs. The most significant barrier is likely to be persuading the majority of the scientific community that PPP enzymes are not too unspecific. Few patents disclosed the rational design of direct PPP ligands, while many inventions relied on long chain peptides-based approaches. Overall, the future of ligands for PPP enzymes as therapeutics seems both challenging and exciting.
