4d08

PDE2a catalytic domain in complex with a brain penetrant inhibitor

spinqualitylabelsall models 4d08, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4d08 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, Q2T, ZN Related: 4d09 Activity: 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PDE2A_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Publication Abstract from PubMed Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a >210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 muM. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders. Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement.,Buijnsters P, De Angelis M, Langlois X, Rombouts FJ, Sanderson W, Tresadern G, Ritchie A, Trabanco AA, VanHoof G, Roosbroeck YV, Andres JI ACS Med Chem Lett. 2014 Jul 22;5(9):1049-53. doi: 10.1021/ml500262u. eCollection , 2014 Sep 11. PMID:25221665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase

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