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PF-3845

现货
Catalog No.
A4374
FAAH抑制剂
组合的产品项目
规格价格库存 数量
200mg
¥ 9,800.00
Ship with 10-15 days
5mg
¥ 550.00
Ship with 10-15 days
10mg
¥ 850.00
Ship with 10-15 days
50mg
¥ 3,300.00
Ship with 10-15 days

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Background

PF-3845 is a highly potent and selective inhibitor of fatty acid amide hydrolase (FAAH) with Ki value of 0.23μM [1].

PF-3845 is a biaryl ether piperidine. It inhibits FAAH by a covalent, irreversible mechanism involving carbamylating FAAH's catalytic S241 nucleophile. It is found that, administration of PF-3845 to mice results a rapid and complete inactivation of FAAH in the brain. PF-3845 is highly selective for FAAH in vivo. It shows no activity to some other serine hydrolases as well as to a FAAH homologue, FAAH2. In addition, PF-3845-treated mice shows significant elevations in brain levels of AEA, other NAEs and liver levels of AEA, PEA and OEA. Moreover, PF-3845 is found to inhibit pain responses in a rat model of inflammatory pain. It is also found to reverse LPS-induced tactile allodynia in mice. This anti-allodynic effect requires activation of both CB1 and CB2 receptors which are the target receptors of the FAAH substrates [1, 2].

References:
[1] Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y, Swaney S, Van Becelaere K, Stevens RC, Cravatt BF. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol. 2009 Apr 24;16(4):411-20.
[2] Booker L, Kinsey SG, Abdullah RA, Blankman JL, Long JZ, Ezzili C, Boger DL, Cravatt BF, Lichtman AH. The fatty acid amide hydrolase (FAAH) inhibitor PF-3845 acts in the nervous system to reverse LPS-induced tactile allodynia in mice. Br J Pharmacol. 2012 Apr;165(8):2485-96.

文献引用

1. Daneva Z, Dempsey SK, et al. "Diuretic, Natriuretic, and Vasodepressor Activity of a Lipid Fraction Enhanced in Medium of Cultured Mouse Medullary Interstitial Cells by a Selective Fatty Acid Amide Hydrolase Inhibitor." J Pharmacol Exp Ther. 2019 Feb;368(2):187-198. PMID:30530623

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt456.46
Cas No.1196109-52-0
FormulaC24H23F3N4O2
SolubilitySoluble in DMSO
Chemical NameN-pyridin-3-yl-4-[[3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]methyl]piperidine-1-carboxamide
SDFDownload SDF
Canonical SMILESC1CN(CCC1CC2=CC(=CC=C2)OC3=NC=C(C=C3)C(F)(F)F)C(=O)NC4=CN=CC=C4
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

动物实验 [1-3]:

动物模型

TBI诱导的雄性缺陷C57BL/6小鼠,炎症性疼痛CFA大鼠模型

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

给药剂量

腹腔注射,TBI后30分钟给药,每日一次,持续3或14天;口服给药,1-30 mg/kg

应用

腹腔注射5 mg/kg剂量的PF3845完全恢复了TBI小鼠在迷宫探索期间成功交替手臂的能力。腹腔注射5 mg/kg及10 mg/kg剂量的PF3845显著减弱TBI引起的焦虑症状,并显著降低TBI诱导的精细运动的缺陷。在炎症性疼痛的大鼠模型中,口服给药1-30 mg/kg剂量的PF-3845以剂量依赖性方式抑制机械性异常性疼痛。在FAAH(-/-)小鼠和野生型小鼠中,腹腔注射1-10 mg/kg剂量的PF-3845诱导抗异常性疼痛表型。足底注射PF-3845(0.1-10μg)增加脑和脊髓中的AEA水平。足底注射PF-3845产生异常性疼痛的部分减少。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Tchantchou F, Tucker L B, Fu A H, et al. The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury[J]. Neuropharmacology, 2014, 85: 427-439.

[2]. Ahn K, Johnson D S, Mileni M, et al. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain[J]. Chemistry & biology, 2009, 16(4): 411-420.

[3]. Booker L, Kinsey S G, Abdullah R A, et al. The fatty acid amide hydrolase (FAAH) inhibitor PF‐3845 acts in the nervous system to reverse LPS‐induced tactile allodynia in mice[J]. British journal of pharmacology, 2012, 165(8): 2485-2496.

生物活性

Description PF-3845 is a selective inhibitor of fatty acid amide hydrolase (FAAH) with Ki value of 0.23 μM.
Targets FAAH          
IC50 0.23 μM (Ki)          

质量控制

质量控制和MSDS

批次:

化学结构

PF-3845

相关生物数据

PF-3845