biostudies-literatureUnknown15(8)Marchesani FThe intricate signaling network within the central nervous system (CNS) involving <i>N</i>-methyl-d-aspartate receptors (NMDARs) has been recognized as a key player in severe neurodegenerative diseases. The indirect modulation of NMDAR-mediated neurotransmission through inhibition of serine racemase (SR)-the enzyme responsible for the synthesis of the NMDAR coagonist d-serine-has been suggested as a therapeutic strategy to treat these conditions. Despite the inherent challenges posed by SR conformational flexibility, a ligand-based drug design strategy has successfully produced a series of potent covalent inhibitors structurally related to amino acid analogues. Among these inhibitors, O-(2-([1,1'-biphenyl]-4-yl)-1-carboxyethyl)hydroxylammonium chloride (<b>28</b>) has emerged as a valuableACS medicinal chemistry letters1298-1305https://www.ebi.ac.uk/biostudies/studies/S-EPMC11318019biostudies-literatureChemical Probes to Investigate Central Nervous System Disorders: Design, Synthesis and Mechanism of Action of a Potent Human Serine Racemase Inhibitor.PMC11318019Bruno SRinaldi SFaggiano SAnnunziato GCostantino GMarchesani FPieroni MCampanini BGiaccari RRebecchi FSpaggiari CfalseChemical Probes to Investigate Central Nervous System Disorders: Design, Synthesis and Mechanism of Action of a Potent Human Serine Racemase Inhibitor.The intricate signaling network within the central nervous system (CNS) involving <i>N</i>-methyl-d-aspartate receptors (NMDARs) has been recognized as a key player in severe neurodegenerative diseases. The indirect modulation of NMDAR-mediated neurotransmission through inhibition of serine racemase (SR)-the enzyme responsible for the synthesis of the NMDAR coagonist d-serine-has been suggested as a therapeutic strategy to treat these conditions. Despite the inherent challenges posed by SR conformational flexibility, a ligand-based drug design strategy has successfully produced a series of potent covalent inhibitors structurally related to amino acid analogues. Among these inhibitors, O-(2-([1,1'-biphenyl]-4-yl)-1-carboxyethyl)hydroxylammonium chloride (<b>28</b>) has emerged as a valuable2024-01-01T00:00:00Z2024 Aug2026-04-12T19:16:20.193Z2026-04-07T13:18:06.626ZS-EPMC113180193914004910.1021/acsmedchemlett.4c00174