García, Ana M.Brea Floriani, José ManuelGonzález García, AlejandroPérez, ConcepciónCadavid Torres, María IsabelLoza García, María IsabelMartínez, AnaGil, Carmen2020-11-022020-11-022017García, A.M.; Brea, J.; González-García, A.; Pérez, C.; Cadavid, M.I.; Loza, M.I.; Martinez, A.; Gil, C. Targeting PDE10A GAF Domain with Small Molecules: A Way for Allosteric Modulation with Anti-Inflammatory Effects. Molecules 2017, 22, 1472http://hdl.handle.net/10347/23530Phosphodiesterase (PDE) enzymes regulate the levels of cyclic nucleotides, cAMP, and/or cGMP, being attractive therapeutic targets. In order to modulate PDE activity in a selective way, we focused our efforts on the search of allosteric modulators. Based on the crystal structure of the PDE10A GAF-B domain, a virtual screening study allowed the discovery of new hits that were also tested experimentally, showing inhibitory activities in the micromolar range. Moreover, these new PDE10A inhibitors were able to decrease the nitrite production in LPS-stimulated cells, thus demonstrating their potential as anti-inflammatory agentseng© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/PDE10 inhibitorsAllosteric modulatorscAMPGAF domainAnti-inflammatoryjournal article10.3390/molecules220914721420-3049open access