scholarly journals Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent α-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

2011 ◽  
Vol 133 (11) ◽  
pp. 4092-4100 ◽  
Author(s):  
Mauro Mileni ◽  
Joie Garfunkle ◽  
Cyrine Ezzili ◽  
Benjamin F. Cravatt ◽  
Raymond C. Stevens ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Enzyme Inhibitor ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Bound State ◽  
Crystallographic Analysis ◽  
X Ray ◽  
Amide Hydrolase ◽  
Reversible Covalent ◽  
Fatty Acid Amide

scholarly journals X-ray Crystallographic Analysis of α-Ketoheterocycle Inhibitors Bound to a Humanized Variant of Fatty Acid Amide Hydrolase

2010 ◽  
Vol 53 (1) ◽  
pp. 230-240 ◽  
Author(s):  
Mauro Mileni ◽  
Joie Garfunkle ◽  
Cyrine Ezzili ◽  
F. Scott Kimball ◽  
Benjamin F. Cravatt ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Crystallographic Analysis ◽  
X Ray ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets

2007 ◽  
Vol 52 (4) ◽  
pp. 1095-1105 ◽  
Author(s):  
Di Zhang ◽  
Anita Saraf ◽  
Teodozyi Kolasa ◽  
Pramila Bhatia ◽  
Guo Zhu Zheng ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Exacerbation of Background Nuclear Cataracts in Sprague-Dawley Rats in Embryo-Fetal Development Studies With JNJ-42165279, a Fatty Acid Amide Hydrolase Inhibitor

2021 ◽  
pp. 019262332110104
Author(s):  
Marjolein van Heerden ◽  
Wendy Roosen ◽  
Sophie Lachau-Durand ◽  
Graham Bailey ◽  
Anthony Ndifor
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
In Utero ◽  
Histological Evaluation ◽  
High Dose ◽  
Lens Fiber ◽  
Sprague Dawley ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Fetal examinations in embryo-fetal developmental (EFD) studies are based on macroscopic and dissecting microscopic evaluations, and histopathology is rarely performed other than to confirm macroscopic findings. Fetal lens examination is therefore generally limited to the presence, size, shape, and color of any abnormality. In a Sprague-Dawley rat EFD study with the fatty acid amide hydrolase (FAAH) inhibitor JNJ-42165279, an unusually high incidence of macroscopic granular foci was noted within the lens of gestation day 21 fetuses across all groups including controls, with higher incidence in the high-dose group. On histological evaluation of the lenses from fetuses with/without gross findings, primary lens fiber hypertrophy (swelling) and degeneration were observed across vehicle- and JNJ-42165279-exposed fetuses. In a follow-up study to investigate the progression or resolution of the fetal lens changes, animals exposed to suprapharmacological doses of JNJ-42165279 in utero had higher incidence of nuclear cataracts as detected via slit-lamp ophthalmic examinations on postnatal days 18 to 21 and 35 to 41. No histologic correlates for these cataracts were identified. We conclude that fetal primary lens fiber hypertrophy and nuclear cataracts at ophthalmology, are common background changes in this rat strain that are exacerbated by in utero exposure to the FAAH inhibitor JNJ-42165279.

Sign in / Sign up

Export Citation Format

Share Document