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An Inhibitor of the Protein Kinases TBK1 and IKK-ɛ Improves Obesity-Related Metabolic Dysfunctions in Mice

An Inhibitor of the Protein Kinases TBK1 and IKK-ɛ Improves Obesity-Related Metabolic Dysfunctions in Mice

Shannon M Reilly, Shian-Huey Chiang, Stuart J Decker, Louise Chang, Maeran Uhm, Martha J Larsen, John R Rubin, Jonathan Mowers, Nicole M White, Irit Hochberg, Michael Downes, Ruth T Yu, Christopher Liddle, etc.

Nat Med. 2013 Mar;19(3):313-21.

PMID: 23396211

Abstract:

Emerging evidence suggests that inflammation provides a link between obesity and insulin resistance. The noncanonical IκB kinases IKK-ɛ and TANK-binding kinase 1 (TBK1) are induced in liver and fat by NF-κB activation upon high-fat diet feeding and in turn initiate a program of counterinflammation that preserves energy storage. Here we report that amlexanox, an approved small-molecule therapeutic presently used in the clinic to treat aphthous ulcers and asthma, is an inhibitor of these kinases. Treatment of obese mice with amlexanox elevates energy expenditure through increased thermogenesis, producing weight loss, improved insulin sensitivity and decreased steatosis. Because of its record of safety in patients, amlexanox may be an interesting candidate for clinical evaluation in the treatment of obesity and related disorders.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP68302578	Amlexanox		68302-57-8	Price

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