PF-04859989 HCl 是不可逆的犬尿氨酸转氨酶KAT II抑制剂，可透过血脑屏障，抑制 hKATⅡ 和 rKATⅡ 的IC50分别为 23 和 263 nM。它对 KATⅡ 的选择性高于人 KATⅠ、KATⅢ 和 KATⅣ (IC50分别为22、11和 >50 μM)。

PF-04859989 HCl is a brain-penetrable and irreversible inhibitor of kynurenine amino transferase II (KAT II), which is the enzyme responsible for most of the brain synthesis of kynurenic acid.

The IC50s values are 23 and 263 nM for hKAT II and rKAT II. PF-04859989 HCl is selective for KAT II over human KAT I, KAT III, and KAT IV (IC50s of 22, 11, and >50 μM, respectively)[3].

Acute administration of the KAT II inhibitor PF-04859989 (5 or 10 mg/kg) was associated with a short-onset, time-dependent decrease in firing rate and burst activity of DA neurons, both parameters reaching a 50% reduction within 45 min. Furthermore, PF-04859989 reduced the number of spontaneously active DA cells as measured 4-6 after administration. Pretreatment with d-cycloserine (30 mg/kg) or CGP-52432 (10 mg/kg) prevented the inhibitory action of PF-04859989 (5 mg/kg) on firing rate and burst firing activity. In contrast, pretreatment with methyllycaconitine (MLA, 4 mg/kg) did not change the response, whereas picrotoxin (4.5 mg/kg) partially prevented the inhibitory effects of PF-04859989 (5 mg/kg, i.v.)[2].

177943-33-8

C9H11ClN2O2

214.65

PF-04859989;PF-04859989HCl;PF04859989;PF 04859989;PF-04859989 HCl

DMSO:100 mg/mL (465.87 mM)
H2O:100 mg/mL (465.87 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years