JNJ-1661010 (C09-0929-732)

InformationJNJ-1661010 JNJ-1661010 (Takeda-25) is a potent and selective FAAH inhibitor with IC50 of 10 nM (rat) and 12 nM (human), exhibits >100-fold selectivity for FAAH-1 when compared to FAAH-2.In vitroFAAH preincubated with JNJ-1661010 suggests a slow reversibility of the interaction between the JNJ-1661010 and the active site, which is accelerated at higher temperatures. JNJ-1661010 is a covalent, mechanism-based substrate inhibitor as examined by LC-ESI-MS. JNJ-1661010 docks with the phenylthiadiazole in the hydrophobic tunnel and the phenylurea in the hydrophilic pocket of FAAH.In vivoJNJ-1661010 (20 mg/kg i.p.) inhibits FAAH by at least 85% for up to 4 h after dosing, resulting accumulation of lipid ethanolamides in rat brain. JNJ-1661010 dose-dependently reverses the tactile allodynia with a maximum efficacy of approximately 90% at 30 min postdose in both Mild Thermal Injury (MTI) mice and rat model. JNJ-1661010 (20 mg/kg) reverses tactile allodynia by 60.8% at 30 min in rat spinal nerve ligation injury model. JNJ-1661010 (50 mg/kg i.p.) shows a significant attenuation of the hyperalgesia at 30 min postdose in rat carrageenan model of inflammatory pain. Rats dosed with JNJ-1661010 (20 mg/kg i.p.) has a plasma Cmax of 26.9 μM at the Tmax of 0.75 h and a Cmax in the brain of 6.04 μM at the Tmax of 2 h. JNJ-1661010 (20 mg/kg i.p.) inhibits brain FAAH and elevates AEA level in brain tissue in rat.Cell Datacell lines：neonatal rat cardiomyocytesConcentrations：Incubation Time：Powder Purity:≥99%. Specification: 10mM in DMSO Molecular Formula: C19H19N5OS Molecular Weight: 365.45