Amlexanox (also known as Aphthasol or aphthous) is a TBK1 and IKK-ε inhibitor. TBK1 and IKK-ε are important enzymes in fatty liver disease, metabolic disorders, and atherosclerosis. Recently, a deuterated form of Amlexanox was developed that increases its stability and half-life. The main indication for non-deuterated Amlexanox was healing of canker sores, which likely required a much shorter half-life. Extending the half-life and stability of Amlexanox by forming deuterated Amlexanox could increase its capacity for use in vivo in diseases such as fatty liver disease, metabolic disorders (i.e. diabetes, obesity), and atherosclerosis.
Compositions and Methods for inhibition of TBK1 and IKK-ε
Amlexanox inhibits TBK1 and IKK-ε by competing for ATP-binding to the enzyme. In vitro MBP kinase assays were used to demonstrate that D-Amlexanox is a TBK1 and IKK-ε inhibitor, likely by out competing ATP-binding, similar to undeuterated Amlexanox. Increasing the stability and half-life of Amlexanox by deuteration will improve its performance and efficacy in vivo. Given the perceived utility of Amlexanox in metabolic disorders, the more stable D-Amlexanox may be an attractive upgrade in performance for treatment of diabetes, obesity, fatty liver disease, and atherosclerosis.
- Treatment of metabolic disorders, fatty liver disease, and atherosclerosis
- Inhibitors of TBK1 and IKK-ε
- Longer half-life than undeuterated Amlexanox
- More stable than undeuterated Amlexanox