TECHNOLOGYWnt Signaling Inhibitors for the Treatment of Diabetes
Overview
The Wnt/β-catenin signaling pathway plays a pivotal role in cell proliferation and differentiation through the regulation of the transcriptional factor β-catenin. The Wnt pathway has been studied extensively for cancer (colon, liver) but the role of the Wnt/β-catenin signaling pathway in diabetes is unknown. UMB researchers have discovered the effect of pyrvinium pamoate to inhibits the Wnt pathway in diabetic mouse models. This technology is a set of novel Wnt/β signaling inhibitors based on the pyrvinium pamoate structure and their method of use for the treatment of diabetes.
Pyrvinium pamoate, a FDA approved, anthelmintic drug for the treatment of Enterobius vermicularis (pinworms), was identified as a potent Wnt/β-catenin pathway inhibitor. Initial proof of concept studies confirmed that pyrvinium injection could significantly improve glucose tolerance and decrease body weight gain in mice fed on a high-fat diet. However, to increase the potency, metabolic stability, and bioavailability of pyrvinium pamoate, novel analogs of pyrvinium pamoate were generated and the lead candidate, YW1149, was identified. Currently, no Wnt/β–catenin pathway inhibitors are clinically available for targeted therapy.
Applications
The global prevalence of diabetes among adults over 18 years has risen from 4.7% in 1980 to 8.5% in 2014. In 2015, an estimated 1.6 million deaths were directly caused by diabetes and another 2.2 million deaths were attributable to high blood glucose in 2012. Due to the widespread reach of the disease, the diabetes market continues to grow. New antidiabetic drugs continue to be developed but older classes of drugs and generics are still widely being used. However, diabetes treatments often lose effectiveness after extended use and require a change in drug or a treatment must be added to the patient’s regimen to manage the chronic disease. The role of the Wnt pathway has been validated for cancer (colon, liver) therapy target, but its role in diabetes is a potential novel target.
Advantages
Novel, potent inhibitor of the Wnt/β–catenin pathway with increased bioavailability and metabolic stability.
Stage of Development
Ongoing in vivo studies with lead compound
Licensing Potential
Available for licensing
Contact Info
Office of Technology Transfer
620 W Lexington St., 4th Floor
Baltimore, MD 21201
Email: [email protected]
Phone: (410) 706-2380
