SCO-792 Enteropeptidase inhibitor

Enteropeptidase is a serine protease, localized to the brush border of the duodenal and jejunal mucosa. It plays a key role in the digestion of proteins to amino acids in mammals. Blood amino acid levels are elevated in patients with diabetes and obesity; therefore, amino acid changes have been suggested to be involved in the development of these diseases. However, the effects of inhibiting protein digestion, thereby decreasing gut amino acid intake in these abnormal metabolic conditions, are largely unknown.

SCOHIA researchers and collaborators identified SCO-792, a new potent orally available enteropeptidase inhibitor, and revealed its therapeutic benefits in improving diabetes and obesity in preclinical studies. Our preclinical studies also showed that enteropeptidase inhibition is highly effective in improving symptoms of diabetes and obesity. In addition, SCO-792 was found to improve liver parameters in a preclinical model of liver-dysfunction. Furthermore, enteropeptidase inhibition improves kidney parameters in preclinical diabetic and non-diabetic kidney disease models. These observations suggest that SCO-792 is likely a novel option for the treatment of diabetes, obesity, non-alcoholic steatohepatitis (NASH), and kidney diseases. Considering the similarity in amino acid changes between enteropeptidase inhibition and surgical gastric bypass, which induces potent therapeutic effects in diabetes, obesity, and NASH, similar mechanisms likely contribute to the therapeutic effects of SCO-792.

Phase 2 proof of concept studies evaluating the therapeutic efficacy of SCO-792 in type 2 diabetes mellitus patients with obesity and in patients with kidney diseases are ongoing.