1. Product Overview
PF-04457845 (CAS 892489-52-0), systematically named N-(furan-3-ylmethyl)-5-(2-oxo-2-((4-phenylpiperazin-1-yl)methyl)pyridin-3-yloxy)pentanamide, is a potent, selective, and irreversible (mechanism-based) inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for degrading the endocannabinoid anandamide (AEA). With the molecular formula C₂₆H₃₂N₄O₄ and a molecular weight of 464.56 g/mol, it appears as a white to off-white solid at room temperature. PF-04457845 inhibits rat and human FAAH with Kᵢ values of 0.3 nM and 0.5 nM respectively, produces >90% FAAH inhibition and significant brain AEA elevation at 0.3 mg/kg po in rats, and exhibits >10,000-fold selectivity over other serine hydrolases including MAGL, COX-1/2, and cannabinoid receptors CB1/CB2. It is a validated clinical-stage (Phase II discontinued) pharmacological tool for studying the endocannabinoid system in pain, anxiety, and neuroinflammation. This product is supplied exclusively for laboratory research use and is not intended for clinical, diagnostic, veterinary, food, or cosmetic applications.
2. Key Features and Advantages
• Ultra-potent irreversible FAAH inhibition: Kᵢ = 0.3 nM (rat FAAH), 0.5 nM (human FAAH); >90% brain FAAH occupancy at 0.3 mg/kg po in rats, with long duration of action (>24 h).
• Exceptional selectivity: >10,000-fold selectivity over MAGL, NAAA, COX-1/2, trypsin, and no significant affinity for CB1/CB2 receptors (up to 10 µM).
• Proven in vivo efficacy: Elevates brain anandamide 2–5 fold, reduces formalin-induced nociception and stress-induced anxiety-like behaviors in validated rodent models.
• High purity: Typically ≥98% by HPLC (suppliers also offer 99.98%), suitable for ex vivo FAAH activity assays, LC-MS/MS quantification of eCBs, and behavioral pharmacology.
• Good solubility: Soluble in DMSO (≥10 mg/mL; prepare 10 mM stock in anhydrous DMSO), also soluble in ethanol and 10% DMSO in PBS (sonication may help); practically insoluble in water.
• Consistent batch quality with supporting analytical data (HPLC, LC-MS, NMR) available; referenced in J. Pharmacol. Exp. Ther. 2012 (Ahn et al.) and multiple pain/anxiety literature.
3. Main Applications
• Endocannabinoid system research: Evaluating FAAH inhibition on brain/tissue anandamide (AEA) and PEA/OEA levels by LC-MS/MS; ex vivo FAAH activity assays from brain homogenates.
• Pain research: Testing antinociceptive effects in acute (hot plate, tail flick), inflammatory (formalin, CFA), and neuropathic (CCI, SNL) pain models in rats and mice.
• Anxiety and depression models: Assessing FAAH blockade on marble burying, elevated plus maze, forced swim test, and social interaction behaviors linked to CB1/Anandamide signaling.
• Neuroinflammation: Investigating FAAH inhibition on microglial activation, cytokine release, and neuroprotective outcomes in LPS or Aβ-exposed primary cultures.
• Medicinal chemistry reference: Used as a benchmark irreversible FAAH inhibitor for SAR comparison with reversible inhibitors (e.g., URB597, PF-3845, BIA 10-2474 analogs).
4. Technical Specifications
5. Storage and Handling
• Store the powdered compound sealed with desiccant, protected from light; recommended storage at -20°C (long term 2–3 years). For DMSO stock solutions, aliquot and store at -80°C wrapped in foil (6 months stable) or -20°C (1 month); avoid repeated freeze–thaw cycles. Typical working stocks are 10 mM in anhydrous DMSO, stored in amber tubes.
• Before opening, allow the sealed vial to warm to room temperature to prevent moisture condensation. Keep container tightly closed when not in use.
• Handle in a well-ventilated area or fume hood. Use personal protective equipment including safety glasses, nitrile gloves, and a lab coat. Avoid inhalation of dust and contact with skin or eyes.
• Intended exclusively for laboratory research by qualified personnel; not for human or veterinary use, food, drug, or cosmetic applications.
6. Safety Overview
• PF-04457845 is a research chemical irreversible FAAH inhibitor with limited toxicological data but known in vivo activity (well tolerated in rodents up to 30 mg/kg; clinical trials showed safety concerns in combination with strong CB1 agonists). Treat as potentially hazardous: may cause irritation to eyes, skin, and respiratory system.
• In case of eye contact, rinse immediately with plenty of running water for at least 15 minutes and seek medical advice. In case of skin contact, wash thoroughly with soap and water.
• If inhaled, move the person to fresh air and keep at rest in a position comfortable for breathing. If ingested, rinse mouth and seek medical attention—do not induce vomiting unless directed by medical personnel.
• Use appropriate engineering controls (fume hood) and personal protective equipment (safety goggles, nitrile gloves, lab coat). Avoid generating dust.
• Dispose of in accordance with local regulations for chemical waste. Do not discharge into drains, waterways, or soil.
• For detailed safety information, refer to the applicable Safety Data Sheet (SDS) prior to handling.
