Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia

• Published in: ACS medicinal chemistry letters Vol. 3; no. 3; pp. 187 - 192
• Main Authors: Dounay, Amy B, Anderson, Marie, Bechle, Bruce M, Campbell, Brian M, Claffey, Michelle M, Evdokimov, Artem, Evrard, Edelweiss, Fonseca, Kari R, Gan, Xinmin, Ghosh, Somraj, Hayward, Matthew M, Horner, Weldon, Kim, Ji-Young, McAllister, Laura A, Pandit, Jayvardhan, Paradis, Vanessa, Parikh, Vinod D, Reese, Matthew R, Rong, SuoBao, Salafia, Michelle A, Schuyten, Katherine, Strick, Christine A, Tuttle, Jamison B, Valentine, James, Wang, Hong, Zawadzke, Laura E, Verhoest, Patrick R
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 08.03.2012; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; hydroxamic acid; KAT II; kynurenine aminotransferase; kynurenic acid; ACID; COVALENT; CRYSTAL-STRUCTURE; CEREBROSPINAL-FLUID; EXTRACELLULAR GLUTAMATE; STRATEGIES; ALIGNMENT; PATHWAY; ELEVATED LEVELS

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...