Peptide
Amlexanox

 

Amlexanox

Amlexanox is an anti-inflammatory and anti-allergic compound which has traditionally been used to treat ulcers by reducing healing time and pain. It has multiple mechanisms of action such as inhibiting inflammation by inhibiting the release of histamine and leukotrienes. It has been shown to selectively inhibit TBK1 and IKK-ε, producing reversible weight loss and improved insulin sensitivity, It is through this mechanism that it has produced substantial results in terms of reducing HbA1C levels and increase insulin sensitivity.

CLINICAL RESEARCH:

Inhibition of IKKε and TBK1 improves glucose control in a subset of patients with type 2 diabetes.Numerous studies indicate an inflammatory link between obesity and type 2 diabetes. The inflammatory kinases IKKε and TBK1 are elevated in obesity; their inhibition in obese mice reduces weight, insulin resistance, fatty liver and inflammation. Here we studied amlexanox, an inhibitor of IKKε/TBK1, in a proof-of-concept randomized, double-blind, placebo-controlled study of 42 obese patients with type 2 diabetes and nonalcoholic fatty liver disease. Treatment of patients with amlexanox produced a statistically significant reduction in Hemoglobin A1c and fructosamine. Interestingly, a subset of drug responders also exhibited improvements in insulin sensitivity and hepatic steatosis. This subgroup was characterized by a distinct inflammatory gene expression signature from biopsied subcutaneous fat at baseline. They also exhibited a unique pattern of gene expression changes in response to amlexanox, consistent with increased energy expenditure. Together, these data suggest that IKKε/TBK1 inhibitors may be effective therapies for metabolic disease in an identifiable subset of patients.

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