PF-04859989 HCl

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-04859989 HCl 是一种可穿透大脑且不可逆的犬尿氨酸氨基转移酶 II (KAT II) 抑制剂，KAT II 是负责大脑中大部分犬尿氨酸合成的酶。

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.(In Vitro):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).(In Vivo):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.).

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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). Rats receiving PF-04859989 (5 mg/kg; i.p.) exhibited a significantly lower number of spontaneously active DA neurons pertrack. Animal Model:Male Sprague-Dawley ratsDosage:5 mg/kg Administration:I.p.Result:Exhibited a significantly lower number of spontaneously active dopamine (DA) neurons pertrack compared to controls.

PF-04859989HCl | PF-04859989 | PF 04859989 | PF04859989

Others

Other Targets

myeloperoxidase

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177943-33-8

286.93

C7H6BrCl2NO2

>98% (HPLC)

In Vitro:?H2O : 100 mg/mL (465.87 mM)

Cl.[O-][N+](=O)c1cccc(Cl)c1CBr

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(-20℃)

With Ice Pack

≥ 2 years