{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["3(3)"],"submitter":["Dounay AB"],"pubmed_abstract":["Kynurenine aminotransferase (KAT) II has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT II. An X-ray crystal structure and (13)C NMR studies of PF-04859989 bound to KAT II have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site. In vivo pharmacokinetic and efficacy studies in rat show that PF-04859989 is a brain-penetrant, irreversible inhibitor and is capable of reducing brain kynurenic acid by 50% at a dose of 10 mg/kg (sc). Preliminary structure-activity relationship inves"],"journal":["ACS medicinal chemistry letters"],"pagination":["187-92"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4025856"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia."],"pmcid":["PMC4025856"],"pubmed_authors":["Hayward MM","Dounay AB","Wang H","Evdokimov A","McAllister LA","Strick CA","Reese MR","Kim JY","Bechle BM","Pandit J","Verhoest PR","Salafia MA","Horner W","Schuyten K","Claffey MM","Anderson M","Campbell BM","Evrard E","Ghosh S","Parikh VD","Rong S","Zawadzke LE","Paradis V","Valentine J","Fonseca KR","Gan X","Tuttle JB"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia.","description":"Kynurenine aminotransferase (KAT) II has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT II. An X-ray crystal structure and (13)C NMR studies of PF-04859989 bound to KAT II have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site. In vivo pharmacokinetic and efficacy studies in rat show that PF-04859989 is a brain-penetrant, irreversible inhibitor and is capable of reducing brain kynurenic acid by 50% at a dose of 10 mg/kg (sc). Preliminary structure-activity relationship inves","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Mar","modification":"2025-04-04T08:42:01.958Z","creation":"2019-03-27T01:28:29Z"},"accession":"S-EPMC4025856","cross_references":{"pubmed":["24900455"],"doi":["10.1021/ml200204m"]}}