Stearoyl-CoA Desaturase-1 (SCD1) inhibition is a novel approach pioneered by Xenon for treating diabetes and obesity.
Mice genetically deficient in the SCD1 gene have the opposite phenotype to metabolic syndrome as they are lean and resistant to weight gain, have improved insulin sensitivity and reduced plasma triglycerides. SCD1 acts like a switch to control fat storage largely determining whether fatty acids are processed for fat deposition (energy storage) or for energy usage. When SCD1 activity is ‘up’, the switch is flipped in the direction of storing fat, and when its activity is ‘down’, the switch is flipped in the direction of burning fat.
We developed a SCD1 biomarker and showed in human clinical validation studies that decreased SCD1 enzyme activity correlated with reduced obesity and cardiovascular risk profile and improved insulin sensitivity. These clinical and genetic data tell us that small molecules inhibiting the activity of SCD1 should replicate these desirable clinical effects and may provide a novel treatment for diabetes, obesity and metabolic syndrome.
We are collaborating with Novartis on development of select SCD1 inhibitors.