5U7L
PDE2 catalytic domain complexed with inhibitors
Summary for 5U7L
| Entry DOI | 10.2210/pdb5u7l/pdb |
| Related | 5U7D 5U7I 5U7J 5U7K |
| Descriptor | cGMP-dependent 3',5'-cyclic phosphodiesterase, (3R)-1-{3-[5-(4-ethylphenyl)-1-methyl-1H-pyrazol-4-yl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl}-N,N-dimethylpyrrolidin-3-amine, ZINC ION, ... (5 entities in total) |
| Functional Keywords | pde2, sbdd, inhibitor, phosphodiesterase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Isoform PDE2A3: Cell membrane ; Lipid-anchor . Isoform PDE2A2: Mitochondrion matrix . Isoform PDE2A1: Cytoplasm . Isoform 5: Mitochondrion : O00408 |
| Total number of polymer chains | 3 |
| Total formula weight | 122236.09 |
| Authors | Pandit, J.,Parris, K. (deposition date: 2016-12-12, release date: 2017-06-28, Last modification date: 2023-10-04) |
| Primary citation | Helal, C.J.,Arnold, E.P.,Boyden, T.L.,Chang, C.,Chappie, T.A.,Fennell, K.F.,Forman, M.D.,Hajos, M.,Harms, J.F.,Hoffman, W.E.,Humphrey, J.M.,Kang, Z.,Kleiman, R.J.,Kormos, B.L.,Lee, C.W.,Lu, J.,Maklad, N.,McDowell, L.,Mente, S.,O'Connor, R.E.,Pandit, J.,Piotrowski, M.,Schmidt, A.W.,Schmidt, C.J.,Ueno, H.,Verhoest, P.R.,Yang, E.X. Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor. J. Med. Chem., 60:5673-5698, 2017 Cited by PubMed Abstract: Phosphodiesterase 2A (PDE2A) inhibitors have been reported to demonstrate in vivo activity in preclinical models of cognition. To more fully explore the biology of PDE2A inhibition, we sought to identify potent PDE2A inhibitors with improved brain penetration as compared to current literature compounds. Applying estimated human dose calculations while simultaneously leveraging synthetically enabled chemistry and structure-based drug design has resulted in a highly potent, selective, brain penetrant compound 71 (PF-05085727) that effects in vivo biochemical changes commensurate with PDE2A inhibition along with behavioral and electrophysiological reversal of the effects of NMDA antagonists in rodents. This data supports the ability of PDE2A inhibitors to potentiate NMDA signaling and their further development for clinical cognition indications. PubMed: 28574706DOI: 10.1021/acs.jmedchem.7b00397 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.38 Å) |
Structure validation
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