Research and Development- AQP9
Liver glucose production in type 2 diabetes - a target for therapy
Type 2 diabetics suffer from an over-production of sugar within the liver, which contributes to high blood glucose levels in patients. Normally, the liver produces and secretes glucose as a response to falling blood glucose levels, but in diabetes patients this mechanism is dysregulated and active at already high levels of glucose. AQP9-targeting therapy is thought to reduce excess glucose production of the liver by inhibiting the transport of glycerol into the liver cell. Glycerol functions as a fuel used in this process (gluconeogenesis). The fact that diabetic mice that lack AQP9 have significantly lower blood glucose levels than diabetic control mice with active AQP9 ( which is able to transport glycerol into liver cell), lends support to the notion that this mechanism can be addressed therapeutically.
Small molecule inhibitors for AQP9- a unique and novel way for treating hyperglycemia
Apoglyx has established a screening platform to identify potent and selective inhibitors for AQP9. A series of such compounds has been generated and the compounds have been tested for their ability to selectively inhibit AQP9 in cell-based assays. Further, it has been demonstrated that the compounds have potential for modification to an entity with properties suitable for clinical use. Several promising candidates are available will be subjected to a rigorous process combining in vitro and in vivo methods to select the best compound for entry into clinical studies. The ultimate aim is to develop a once-daily, oral therapy for diabetes patients.