A New Old Diabetes and Obesity Drug Candidate

Obesity is a therapeutic area that has broken a lot of hearts (and wallets) over the years. A scroll back through this category will show some of the wreckage, and there's plenty more out there. But hope does that springing-eternal thing that it does, and there's an intriguing new possibility for a target in this area. Alan Saltiel of Michigan (whose group has had a long presence in this sort of research), along with a number of other well-known collaborators, report work on the inflammation connection between diabetes and obesity: Although the molecular events underlying the relationship between obesity and insulin resistance remain uncertain, numerous studies have implicated an inflammatory link. Obesity produces a state of chronic, low-grade inflammation in liver and fat accompanied by the local secretion of cytokines and chemokines that attenuate insulin action. Knockout or pharmacological inhibition of inflammatory pathways can disrupt the link between genetic- or diet-induced obesity and insulin resistance, suggesting that local inflammation is a key step in the generation of cellular resistance to important hormones that regulate metabolism. Saltiel's lab had already implicated IKK-epsilon as a kinase involved in this pathway in obese mouse models, and they've been searching for small-molecule inhibitors of it. As it turns out, a known compound (amlexanox) with an uncertain mechanism of action is such an inhibitor. It's best-known, if it's known at all, as a topical ...
Source: In the Pipeline - Category: Chemists Tags: Diabetes and Obesity Source Type: blogs