RT Journal Article
T1 Targeting PDE10A GAF Domain with Small Molecules: A Way for Allosteric Modulation with Anti-Inflammatory Effects
A1 García, Ana M.
A1 Brea Floriani, José Manuel
A1 González García, Alejandro
A1 Pérez, Concepción
A1 Cadavid Torres, María Isabel
A1 Loza García, María Isabel
A1 Martínez, Ana
A1 Gil, Carmen
K1 PDE10 inhibitors
K1 Allosteric modulators
K1 cAMP
K1 GAF domain
K1 Anti-inflammatory
AB Phosphodiesterase (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 agents
PB MDPI
YR 2017
FD 2017
LK http://hdl.handle.net/10347/23530
UL http://hdl.handle.net/10347/23530
LA eng
NO García, 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, 1472
NO Financial support from MINECO and FEDER founds (UE program) (project SAF2012-33600) is acknowledged. A.M.G. acknowledges pre-doctoral grants to the CSIC (JAEPre program)
DS Minerva
RD 25 abr 2026