Description:
Project ID: D2020-28
Background
Based upon the success of a mixture of simvastatin (SIM) + metformin (Met) + digoxin (Dig), dubbed “C3”, for treating pancreatic ductal adenocarcinoma (PDAC) via a pleiotropic mechanism where attenuation of the BIRC5 pathway is a major component, we have pursued novel, single-molecular constructs that combine features of a statin and a biguanide (Met-like) derivative.
From a family of about 10 analogs, we identified Sim-Met (SM) and Lov-Met (LM) to be inhibitors of the BIRC5 pathway and effective anticancer agents in cell culture studies. Furthermore, some human PDAC biopsy cultures were effectively treated without also adding Dig, suggesting the potential value for personalized therapy using our combination drugs with and without added Dig subsequent to assessment by clinical biopsy.
Because a statin + Met are used to treat metabolic disorders, we also investigated our novel, single-molecule versions SM and LM as possible therapy for these types of indications. A preliminary in vivo study suggests that LM, in particular, may have some distinctive beneficial properties. As such it is presently regarded as our lead compound
Invention Description
Researchers at the University of Toledo in addition with other collaborators have discovered novel prodrug and novel single hybrid drug combinations of metformin analogs connected to statin analogs that can attenuate the PDX1-BIRC5-Survivin axis in a manner conducive to treating metabolic disorders such as diabetes, hyperlipidemia, metabolic syndrome, certain cardiovascular abnormalities, cancers including PDAC in particular, and viral illnesses including COVID-19.
Applications
- A novel, potent, and patented therapy of PDAC and similar cancers.
Advantages
- The C3 compounds have enhanced anti-tumor effects by targeting BIRC5.
- Both types inhibit cell proliferation of PDAC cells in vitro and in vivo via suppression of BIRC5 expression.
- The compounds described in our patented approach are either single molecule drug constructs having pleotropic effects or are dual prodrugs that release two single drug molecules that simultaneously display their own effects.
IP Status: Patent Pending Domestic and International
