product name PF-3845
Description: PF-3845 is a highly potent, selective and irreversible inhibitor of FAAH with Ki of 230 nM, it showed little activity against FAAH2. Structurally, PF-3845 is a biaryl ether piperidine. It inhibits FAAH by a covalent, irreversible mechanism involving carbamylating FAAHs catalytic S241 nucleophile. PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury.
References: Chem Biol. 2009 Apr 24;16(4):411-20; Br J Pharmacol. 2012 Apr;165(8):2485-96.
456.46
Formula
C24H23F3N4O2
CAS No.
1196109-52-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 91 mg/mL (199.4 mM)
Water: <1 mg/mL
Ethanol: 91 mg/mL (199.4 mM)
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 15mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19419999
| In Vitro |
In vitro activity: PF-3845 selectively inhibits FAAH by carbamylating FAAHs serine nucleophile. Kinase Assay: Cell Assay: |
|---|---|
| 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. PF-3845 shows a long duration of action up to 24 hour. PF-3845-treated mice also shows dramatic (>10-fold) elevation in brain levels of AEA and other NAEs (N-pamitoyl ethanolamine [PEA] and N-oleoyl ethanolamine [OEA]). FAAH is AEA-degrading enzyme fatty acid amide hydrolase. PF-3845 (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 PF-3845). At higher doses (10 and 30 mg/kg), PF-3845 inhibits pain responses to an equivalent, if not greater, degree than the nonsteroidal anti-inflammatory drug naproxen (10mg/kg, p.o.). PF-3845 (10 mg/kg, i.p.) significantly reverses LPS-induced tactile allodynia, but doesnt modify paw withdrawal thresholds in the saline-injected paw. |
| Animal model | Male C57BL/6 mice |
| Formulation & Dosage | Dissolved in a solution of 18:1:1 v/v/v saline:emulphor:ethanol.; 10 mg/kg or 1-30 mg/kg; i.p. or p.o. administration |
| References | Chem Biol. 2009 Apr 24;16(4):411-20; Br J Pharmacol. 2012 Apr;165(8):2485-96. |
