PF-04859989 is an inhibitor of kynurenine aminotransferase II (KAT II; IC50s = 0.032 and 0.263 µM for human and rat recombinant enzymes, respectively).1 It is selective for KAT II over KAT I, -III, and -IV (IC50s = 21.6, 107, and >50 µM, respectively). In vivo, PF-04859989 (10 mg/kg, s.c.) reduces basal striatum, prefrontal cortex, and hippocampus kynurenic acid levels in rats. It prevents ketamine- or amphetamine-induced disruption of auditory gating in rats, as well as prevents ketamine-induced deficits in spatial memory in non-human primates. PF-04859989 also inhibits glutamate oxaloacetate transaminase 1 (GOT1; IC50 = 8 µM) and reduces the viability of PaTu 8988t and PaTu 8902 pancreatic cancer cells in a concentration-dependent manner.2
1.Kozak, R., Campbell, B.M., Strick, C.A., et al.Reduction of brain kynurenic acid improves cognitive functionJ. Neurosci.34(32)10592-10602(2014) 2.Yoshida, T., Yamasaki, S., Kaneko, O., et al.A covalent small molecule inhibitor of glutamate-oxaloacetate transaminase 1 impairs pancreatic cancer growthBiochem. Biophys. Res. Commun.522(3)633-638(2020)