PF-04457845

PF-04457845 is a greatly and effctive FAAH inhibitor, and for hFAAH (IC50=7.2±0.63 nM) and rFAAH (IC50=7.4±0.62 nM) . (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) . PF-04457845 has exquisite selectivity for FAAH relative to other members of the serine hydrolase superfamily as demonstrated by competitive activity-based protein profiling. PF-04457845 completely inhibits FAAH in human and mouse membrane proteomes at both 10 and 100 μM with no off targets. PF-04457845 is completely selective for FAAH, and none of the other FP-reactive serine hydrolases in the tested tissues are inhibited by PF-04457845 even at 100 μM. (In Vivo) :Oral administration of PF-04457845 at 0.1 mg/kg results in efficacy comparable to that of naproxen at 10 mg/kg in a rat model of inflammatory pain. 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. Furthermore, at 0.1 mg/kg (p.o.), PF-04457845 inhibits the pain response to a comparable degree as the nonsteroidal anti-inflammatory drug naproxen at 10 mg/kg. FAAH is confirmed to be completely inhibited in mice treated with PF-04457845 at 1 and 10 mg/kg p.o. by competitive activity-based protein profiling (ABPP) study.

1020315-31-4

>98% (HPLC)

DMSO : ≥ 100 mg/mL 219.57 mM

C1CN (CCC1=CC2=CC (=CC=C2) OC3=NC=C (C=C3) C (F) (F) F) C (=O) NC4=NN=CC=C4

C23H20F3N5O2

455.44

Storage temperature: -20°C. Stability: ≥ 2 years