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JNJ-31020028

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Chemical Structure| 1094873-14-9 同义名 : -
CAS号 : 1094873-14-9
货号 : A136309
分子式 : C34H36FN5O2
纯度 : 98%
分子量 : 565.68
MDL号 : MFCD18782744
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(35.36 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Neuropeptide Y (NPY) is abundantly distributed in the peripheral and central nervous system (CNS) and is involved in the control of sympathetic nervous system activity, immune function, central regulation of energy balance and food intake,stress, anxiety, mood, and cognition[3]. JNJ-31020028 is a novel high affinity and low molecular weight Y2 receptor antagonist. NPY inhibits hypothalamic NE release through the Y2 receptor, acting at both the NE terminal and cell body region ,and Y2 antagonists increase NE release from hypothalamic synaptosomes[4]. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of NPY Y2 antagonism[5]. The compound had poor oral bioavailability (6%) but high subcutaneous bioavailability (100%).Subcutaneous dosing was the preferred route for several of the models described in this paper and yielded good plasma levels (Cmax 4.35μmol/l) and fast absorption with a 0.83-h half-life[6].In autoradiography studies, N-(11)C-methyl-JNJ-31020028 receptor binding sites were observed primarily in the hippocampus and were inhibited by unlabeled JNJ-31020028. In PET studies, N-(11)C-methyl-JNJ-31020028 was metabolized slowly in the bloodstream, with 25% of the (11)C-labeled parent compound remaining 30 min after injection. PET imaging showed baseline binding potentials of 0.64 ± 0.07 in the thalamus, 0.55 ± 0.02 in the caudate, and 0.49 ± 0.03 in the hippocampus. Graphical reference region analyses demonstrated that N-(11)C-methyl-JNJ-31020028 binding was reversible; infusion of unlabeled JNJ-31020028 markedly displaced the PET radioligand from binding sites in the hippocampus, thalamus, caudate nucleus, and cerebellum but not in the corpus callosum, which served as reference region for nonspecific binding[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.77mL

0.35mL

0.18mL

8.84mL

1.77mL

0.88mL

17.68mL

3.54mL

1.77mL
参考文献

[1]Cippitelli A, Rezvani AH, et al. The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety. Alcohol. 2011 Sep;45(6):567-76.

[2]Shoblock JR, Welty N, et al. In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl] piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y(2) receptor. Psychopharmacology (Berl). 2010 Feb;208(2):265-77.

[3] Heilig M (2004) The NPY system in stress, anxiety and depression.Neuropeptides 38:213–224

[4] Brennauer A, Dove S, Buschauer A (2004) Structure–activity relationships of nonpeptide neuropeptide Y receptor antagonists.Handb Exp Pharmacol 162:505–546

[5] Andrea Cippitelli,et al. The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety. Alcohol. 2011 Sep;45(6):567-76.

[6] James R Shoblock ,et al. Psychopharmacology (Berl). 2010 Feb;208(2):265-77.

[7]Michael Winterdahl,et al. PET brain imaging of neuropeptide Y2 receptors using N-11C-methyl-JNJ-31020028 in pigs{{Michael Winterdahl,et al. PET brain imaging of neuropeptide Y2 receptors using N-11C-methyl-JNJ-31020028 in pigs. J Nucl Med. 2014 Apr;55(4):635-9.