Summary for 9GIF
| Entry DOI | 10.2210/pdb9gif/pdb |
| Descriptor | Glutamate receptor ionotropic, NMDA 1, (2~{R})-2-azanyl-3-(2~{H}-thiophen-5-ylcarbonylamino)propanoic acid, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | ion transport ligand gated ion channel, transport protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 33734.46 |
| Authors | Carr, K.H.,Ascic, E.,Leonard, P.M. (deposition date: 2024-08-19, release date: 2024-11-27, Last modification date: 2024-12-11) |
| Primary citation | Ascic, E.,Marigo, M.,David, L.,Frisch Herrik, K.,Grupe, M.,Hougaard, C.,Mork, A.,Jones, C.R.,Badolo, L.,Frederiksen, K.,Boonen, H.C.M.,Jensen, H.S.,Kilburn, J.P. Advancements in NMDA Receptor-Targeted Antidepressants: From d-Cycloserine Discovery to Preclinical Efficacy of Lu AF90103. J.Med.Chem., 67:20135-20155, 2024 Cited by PubMed Abstract: The discovery of d-cycloserine (), a partial agonist of the NMDA receptor that exhibits antidepressant effects without the psychotomimetic effects of ketamine, has fueled interest in new NMDA-targeting antidepressants. Our objective was to identify potent partial agonists mirroring , particularly tailored for the GluN2B subtype of the NMDA receptor. Through a structure-based drug design approach, we discovered compound . This compound acts as a partial agonist of the GluN1/GluN2B complex, exhibiting 24% efficacy, and has an EC value of 78 nM. Subsequent investigations led us to (Lu AF90103), a methyl ester prodrug of capable of penetrating the blood-brain barrier, as confirmed by rat microdialysis studies. In different rat models relevant to neuropsychiatric diseases, administering led to demonstrating both acute effects, observed in a seizure model and EEG, and lasting effects in the stress-sensitive hippocampal pathway and an antidepressant-sensitive model. PubMed: 39560374DOI: 10.1021/acs.jmedchem.4c01477 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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