PF-3845

製品コードS2666 バッチS266603

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₄H₂₃F₃N₄O₂

分子量

456.46

CAS No.

1196109-52-0

Solubility (25°C)*

体外

DMSO

91 mg/mL (199.36 mM)

Ethanol

91 mg/mL (199.36 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	15.000mg/ml (32.86mM)	Taking the 1 mL working solution as an example, add 300 μL of 50 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	PF-3845 is a potent, selective and irreversible FAAH inhibitor with K_i of 230 nM, showing negligible activity against FAAH2.
in vitro	PF-3845 selectively inhibits FAAH by carbamylating FAAH's serine nucleophile. ^[1]
in vivo	PF-3845 treated mice (10 mg/kg, i.p.) shows rapid and complete inactivation of FAAH in the brain, as judged by competitive activity-based protein profiling (ABPP) with the serine hydrolase-directed probe fluorophosphonate (FP)-rhodamine. This compound shows a long duration of action up to 24 hour. This compound-treated mice also shows dramatic (>10-fold) elevation in brain levels of AEA and other NAEs ( [PEA] and [OEA]). FAAH is AEA-degrading enzyme fatty acid amide hydrolase. This chemical (1–30 mg/kg, oral administration [p.o.]) causes a dose dependent inhibition of mechanical allodynia with a minimum effective dose (MED) of 3 mg/kg (rats are analyzed at 4 hour post dosing with this chemical). At higher doses (10 and 30 mg/kg), this compound inhibits pain responses to an equivalent, if not greater, degree than the nonsteroidal anti-inflammatory drug naproxen (10mg/kg, p.o.). ^[1] This chemical (10 mg/kg, i.p.) significantly reverses LPS-induced tactile allodynia, but doesn't modify paw withdrawal thresholds in the saline-injected paw. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	FAAH Assay
キナーゼアッセイ	The GDH-coupled FAAH assay is performed for determination of potencies (K_inact/ K_i values) of irreversible inhibitors. For the development of structure-activity relationship,the FAAH assay is performed in 384-well microplates with a final volume of 50μL. In the 384-well format assay, the overall potency, K_inact/ K_i values, are generally calculated from the slope, K_inact/[ K_i (1 + [S]/ K_m)], which is obtained from the kobs versus [I] linear lines under the conditions of [I] << K_i as described (from the kobs values fitted to equation 3 in PNAS 2008). In order to obtainK_inact and K_i values separately for this compound and URB597, the FAAH assay is performed in the 96-well format with a final volume of 200μL. Due to its more frequent reading capabilities (every 10 and 30 seconds for the 96- and 384-well formats, respectively), the 96- well format allows a measurement of K_obs values at higher concentrations of inhibitors. The K_inact and K_i values are obtained by fitting the kobs versus [I] curves to the equation, K_obs = K_inact [I]/{[I] + K_i (1 + [S]/ K_m}. FAAH inactivation rates in the absence of inhibitors are subtracted from all kobs values obtained in the presence of inhibitors. The ratio K_inact/ K_i calculated from the individual K_inact and K_i values obtained separately agrees well with the K_inact/ K_i value obtained from the slope described above.
動物実験	動物モデル	Male C57BL/6 mice
	投薬量	10 mg/kg or 1-30 mg/kg
	投与方法	Administered via i.p. 1 hour before sacrificed by CO₂ or oral administration.

参考

https://pubmed.ncbi.nlm.nih.gov/19389627/
https://pubmed.ncbi.nlm.nih.gov/21506952/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Cooperative Enzymatic Control of N-acyl Amino Acids by PM20D1 and FAAH [ Elife, 2020, 9;9:e55211]	PubMed: 32271712
Modulation of Pain Sensitivity by Chronic Consumption of Highly Palatable Food Followed by Abstinence: Emerging Role of Fatty Acid Amide Hydrolase. [ Front Pharmacol, 2020, 11:266]	PubMed: 32231568
The fatty-acid amide hydrolase inhibitor URB597 inhibits MICA/B shedding [ Sci Rep, 2020, 10(1):15556]	PubMed: 32968163
Bioluminescent cell-based NAD(P)/NAD(P)H assays for rapid dinucleotide measurement and inhibitor screening [ Assay Drug Dev Technol, 2014, 12(9-10):514-26]	PubMed: 25506801

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。