5VP0

Discovery of Clinical Candidate N-{(1S)-1-[3-Fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders

Summary for 5VP0

• Entry DOI: 10.2210/pdb5vp0/pdb
• Related: 5VP1
• Descriptor: cGMP-dependent 3',5'-cyclic phosphodiesterase, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: inhibitor, phosphodiesterase, brain-pentrating, cognitive disorders, 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: 122340.39

Authors

Hoffman, I.D. (deposition date: 2017-05-03, release date: 2017-08-23, Last modification date: 2024-03-13)

• Primary citation: Mikami, S.,Nakamura, S.,Ashizawa, T.,Nomura, I.,Kawasaki, M.,Sasaki, S.,Oki, H.,Kokubo, H.,Hoffman, I.D.,Zou, H.,Uchiyama, N.,Nakashima, K.,Kamiguchi, N.,Imada, H.,Suzuki, N.,Iwashita, H.,Taniguchi, T.; Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders.; J. Med. Chem., 60:7677-7702, 2017; PubMed: 28796496; DOI: 10.1021/acs.jmedchem.7b00807

Experimental method

X-RAY DIFFRACTION (2.2 Å)