PF-04457845

SKU: orb1302952

Description

PF-04457845 is a potent and selective FAAH inhibitor, exhibiting high efficacy against both human (IC50=7.2 nM) and rat (IC50=7.4 nM) enzymes. It is a valuable research tool for studying endocannabinoid signaling in preclinical models of pain, inflammation, and neurological disorders.

Research Area

Cell Biology, Metabolism Research, Neuroscience

Key Properties

• CAS Number: 1020315-31-4
• MW: 455.43
• Purity: 100.00%
• Formula: C₂₃H₂₀F₃N₅O₂
• SMILES: FC(F)(F)c1ccc(Oc2cccc(C=C3CCN(CC3)C(=O)Nc3cccnn3)c2)nc1
• Target: Autophagy,FAAH
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:2.5 mg/mL (5.49 mM);DMSO:50 mg/mL (109.79 mM)

Bioactivity

• Target IC50:
  FAAH (rat):7.4±0.62 nM|FAAH (human):7.2±0.63 nM
• In Vivo:
  In a rat model, oral administration of PF-04457845 causes a significant inhibition of mechanical allodynia measured after 4 h with a minimum effective dose (MED) of 0.1 mg/kg. FAAH is confirmed to be completely inhibited in mice treated with PF-04457845(1 and 10 mg/kg p.o.).
• In Vitro:
  PF-04457845 inhibits FAAH by a covalent, irreversible mechanism involving carbamylation of the active-site serine nucleophile of FAAH with high in vitro potency (kinact/Ki and IC50 values of 40300 M-1s-1 and 7.2 nM, respectively, for human FAAH).
• Cell Research:
  PF-04457845 is formulated as a nanocrystalline suspension in 2% polyvinylpyrrolidone and 0.15% sodium dodecyl sulfate in H2O (Rats). PF-04457845 is prepared in polyethyleneglycol 300 (Mice).RatsPF-04457845 is administered orally to male Sprague-Dawley rats (200 g-250 g) at the indicated dose (mg/kg) as a nanocrystalline suspension in 2% polyvinylpyrrolidone and 0.15% sodium dodecyl sulfate in H2O. The dose volume is 10 mL/kg. The Paw Withdrawal Threshold (PWT) is evaluated at 4 h post dose. PWT measurements are averaged and statistical comparisons between groups are made using analysis of variance and unpaired T-tests.Mice Male C57BL6/J mice (7 weeks old; n=8) are treated with PF-04457845 (1 or 10 mg/kg in polyethyleneglycol 300 vehicle by oral administration in a volume of 4 mL/kg), the synthetic cannabinoid agonist WIN 55,212-2 (1 or 10 mg/kg in 18:1:1 saline/Emulphor/ethanol vehicle by intraperitoneal administration in a volume of 10 mL/kg), or the corresponding vehicle. Mice are evaluated for hypomotility, hypothermia, antinociceptive, and cataleptic effects at 4 h or 30 min after PF-04457845 or WIN 55,212-2 administration, respectively, using the tetrad tests except that catalepsy is assessed for 60 s instead of 10 s. Statistical analysis is performed using the Student's t test comparing each treatment group with vehicle.
• Animal Research:
  Male C57BL6/J mice (7 weeks old) are treated with PF-04457845 (1 or 10 mg/kg in polyethyleneglycol 300 vehicle by oral administration in a volume of 4 mL/kg).

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Autophagy, inhibit, Inhibitor, hFAAH, FAAH, Fatty acid amide hydrolase, rFAAH, PF 04457845, PF04457845, PF-04457845

Compound Identifiers

PubChem CID

24771824