Venenum Biodesign

A Member of Genesis Biotechnology Group

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The public health crisis over the prevalence of type II diabetes mellitus (T2DM) and its role in cardiovascular disease has led many pharmaceutical and biotech companies to invest in new therapies.  TGR5 is a cell-surface G protein-coupled receptor that is activated by bile acids, and as such is involved in regulating lipid, glucose, and energy metabolism. It has been demonstrated that BA activation of TGR5 induces GLP-1 release from enteroendocrine L cells. The therapeutic relevance of GLP-1 is established by the efficacy of drugs for T2DM such as Byetta (Exenatide) and other GLP-1 analogs. While efficacious, these incretin mimetics require either daily or weekly administration by subcutaneous injection. We hypothesize that activation of TGR5 by an orally active, small molecule agonist would result in the stimulation of enteroendocrine L cells to secrete GLP-1 and thereby could result in a less invasive way to increase GLP-1 levels and lower blood glucose. Our strategy is develop small molecule agonists with minimal systemic exposure.

TGR5 Agonists

Our small molecule compound series activates both human and mouse TGR5 receptors facilitating testing in relevant murine models. Oral delivery of compounds that have very low systemic exposure trigger a significant rise in GLP-1 and reduction in the glucose excursion. Current efforts are to further enhance the in vitro and in vivo activities in chronic animal disease models, while maintaining low systemic exposure.