product name JNJ-1661010
Description: JNJ-1661010 (also known as Takeda-25) is a potent and selective, reversible FAAH inhibitor with IC50 of 10 nM (rat) and 12 nM (human), exhibits >100-fold selectivity for FAAH-1 when compared to FAAH-2. JNJ-1661010 is a piperazinyl phenyl urea with its structure distinct from alkylcarbamic acid esters and α–ketoheterocyclic compounds. JNJ-1661010 is a brain penetrant and active in vivo. Inhibition of FAAH by JNJ-1661010 is reversible through the hydrolysis of the carbamate leading to the release of the piperazinyl fragment and the restoration of enzymatic functionality of FAAH.
References: Bioorg Med Chem Lett. 2008 Sep 1;18(17):4838-43; Anesth Analg. 2009 Jan;108(1):316-29.
365.45
Formula
C19H19N5OS
CAS No.
681136-29-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 36 mg/mL (98.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+95% Corn oil: 5 mg/mL
Synonyms
Takeda-25
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420059
| In Vitro |
In vitro activity: FAAH 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. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | JNJ-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. |
| Animal model | Mild Thermal Injury (MTI) mice and rat models |
| Formulation & Dosage | Dissolved in 5% Pharmasolve: 20% Cremophor: 75% saline; 50 mg/kg; i.p. injection |
| References | Bioorg Med Chem Lett. 2008 Sep 1;18(17):4838-43; Anesth Analg. 2009 Jan;108(1):316-29. |
