SAR approach: Computer identified structure-activity relationships to known NAD(P)H-oxidase inhibitors has produced a set of novel inhibitory compounds. These have been found to lower blood glucose levels and improve insulin sensitivity in diabetic animals. Thus proof of principle has been obtained in accordance with convincing literature.
HTS approach: High throughput screening of chemicals for NOX4 inhibition resulted in 700 hits that were funnelled down 20 promising compounds. The project is in hit-to-lead phase and selectivity against NOX2 has been established for a number of development compounds.
In-licensing approach: A candidate drug (CD) has been inlicensed from Swedish Orphan Biovitrum. It is effective in decreasing food intake, body weight, blood glucose and insulin levels in animal models of obesity. It acts on both peripheral tissues and in CNS and it acts as an activator of the large conductance KATP channel.
Identification of genetic markers: A project has been initiated for the identification of patient subpopulations genetically prone to increased sensitivity to reactive oxygen species and the development of screening procedures for identification of diabetes patients particularly benefitting from NOX4 inhibition.
The role of NAD(P)H-oxidase in different indications