Background:

JNJ-42165279 is a potent and irreversible inhibitor of fatty acid amide hydrolase (FAAH) [1]. JNJ-42165279 covalently inactivates the FAAH enzyme [1]. JNJ-42165279 is highly selective with regard to other enzymes, ion channels, transporters, and receptors. The fatty acid amide hydrolase interrupt the actions through degrading various endogenous lipid signaling molecules. FAAH degrades several fatty acid ethanolamides rapidly, such as FAAH’s primary substrate, AEA (N-arachidonyl ethanolamide or anandamide), PEA (N-palmitoyl ethanolamide), and OEA (N-oleoyl ethanolamide) [1].

In vitro: JNJ-42165279 inhibited recombinant human and rat FAAH with the IC50s of 70 ± 8 nM and 313 ± 28 nM, respectively [1]. JNJ-42165279 (10 μM) exhibited high selectivity against a panel of receptors, enzymes, transporters, and ion-channels. JNJ-42165279 (10 μM) showed no inhibitory effects against CYPS (1A2, 2C8, 2C9, 2C19, 2D6, 3A4) or hERG [1].

In vivo: In the rat spinal nerve ligation (SNL or Chung) model of neuropathic pain, JNJ-42165279 exhibited analgesic properties. JNJ-42165279 dose-dependently reversed the robust tactile allodynia. The ED90 was 22 mg/kg, which corresponds to a plasma concentration of 2.5 μM at 30 min [1].

参考文献:
[1] Keith J M, Jones W M, Tichenor M, et al.  Preclinical characterization of the FAAH inhibitor JNJ-42165279[J]. ACS medicinal chemistry letters, 2015, 6(12): 1204-1208.