Novel Inhibitors of N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA)

Tech ID: 18747 / UC Case 2007-532-0

Background

Ethanoloamides of long-chain fatty acids, termed N-acylethanolamines (NAEs) have been reported to have a variety of biological activities. NAEs are a substrate of N-acylethanolamine-hydrolyzing acid amidase (NAAA) that catalytically hydrolyze NAEs to ethanolamine and the corresponding fatty acid. The catalytic activity of NAAA is distinct from that of fatty acid amide hydrolase (FAAH) and NAAA exhibits a preference for N-palmitoylethanolamine (PEA) over other NAEs. PEA has anti-inflammatory, anti-nociceptive, immunosuppressive, neuroprotective and also anti-oxidant activity. These characteristics make NAAA an excellent therapeutic target for discovery of novel compounds to treat pain, inflammation, and other conditions that may benefit from modulating the levels of endogenous fatty-acid ethanolamides, particularly PEA.

Technology Description

Current analgesic and anti-inflammatory agents produce side effects, limited efficacy and there remains an unmet need for new therapeutics for pain and inflammatory disorders. UC Irvine investigators have discovered a new class of compounds that inhibit N-acylethanolamine-hydrolyzing acid amidase (NAAA). Several novel NAAA inhibitors showed submicromolar activity in vitro enzymatic assays. Potent and selective compounds were further evaluated for anti-inflammatory effects in animal models. An increase in PEA levels, modulation of the immune cell infiltrate, and a reduction in inflammation were demonstrated. NAAA inhibitors will be useful to alleviate conditions associated with a reduced concentration of N-palmitoylethanolamine (PEA), such as pain and inflammation, and neurodegenerative disorders.

Applications

Various NAAA inhibitors were identified that will be useful in the treatment of conditions associated with reduced levels of endogenous ethanolamides. NAAA inhibitors represent therapeutic agents for the treatment of inflammatory diseases (rheumatoid arthritis, osteoarthritis, asthma, psoriasis), pain, metabolic diseases, and neurodegenerative diseases such as Alzheimer's Disease.

Patent Status

Country Type Number Dated Case
Canada Issued Patent 2856522 10/27/2020 2011-057
United States Of America Issued Patent 10,363,237 07/30/2019 2007-532
United States Of America Issued Patent 9,908,848 03/06/2018 2011-056
Japan Issued Patent 6266528 01/05/2018 2011-057
Australia Issued Patent 2012340519 01/03/2018 2011-057
United States Of America Issued Patent 9,828,338 11/28/2017 2013-109
Germany Issued Patent 2782567 03/22/2017 2011-057
France Issued Patent 2782567 03/22/2017 2011-057
United Kingdom Issued Patent 2782567 03/22/2017 2011-057
Italy Issued Patent 2782567 03/22/2017 2011-057
United States Of America Issued Patent 9,353,075 05/31/2016 2011-057
United States Of America Published Application 20100311711 12/09/2010 2007-532
 

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