title: Preclinical Characterization of the FAAH Inhibitor JNJ-42165279.
abstract: The pre-clinical characterization of the aryl piperazinyl urea inhibitor of fatty acid amide hydrolase (FAAH) JNJ-42165279 is described. JNJ-42165279 covalently inactivates the FAAH enzyme, but is highly selective with regard to other enzymes, ion channels, transporters, and receptors. JNJ-42165279 exhibited excellent ADME and pharmacodynamic properties as evidenced by its ability to block FAAH in the brain and periphery of rats and thereby cause an elevation of the concentrations of anandamide (AEA), oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA). The compound was also efficacious in the spinal nerve ligation (SNL) model of neuropathic pain. The combination of good physical, ADME, and PD properties of JNJ-42165279 supported it entering the clinical portfolio.
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Keith
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Jones
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Tichenor
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Seierstad
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Palmer
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Webb
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Karbarz
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Scott
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Sandy J
authors.initials: SJ
authors.lastname: Wilson
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Wennerholm
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Leon
authors.initials: L
authors.lastname: Chang
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Rizzolio
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Rynberg
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Chaplan
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: J Guy
authors.initials: JG
authors.lastname: Breitenbucher
keywords: FAAH; anandamide; covalent; enzyme; ethanolamides