E-7869 (R-flurbiprofen) is a pharmacologic “cousin” of ibuprofen, the well-known non-steroidal antiinflammatory drug (NSAID) that has been prescribed internationally since 1976. Like many chemical compounds, flurbiprofen and other NSAIDs exist in two structural forms that are “mirror images” of each other. These structural forms, called the R-enantiomer and the S-enantiomer, share the same chemical formula, but may have the potential for different pharmacologic activity. In the past, studies with  both enantiomeric forms of the NSAIDS had proven that this class of medications demonstrated significant antiinflammatory, and potentially anti-cancer, and anti-Alzheimer’s activity. However, clinical development of the S-enantiomers in these therapeutic areas was significantly hindered by an undesirable safety profile, especially by the potential for severe gastrointestinal problems.

Unlike the irritating S-enantiomers, R-enantiomers of the NSAIDs were found to have no detectable gastrointestinal side effects. However, their anti-cancer and anti-Alzheimer’s activity remained unknown. To delineate the pharmacological activity of the R-enantiomers, EncorePharma Laboratory scientists followed an innovative mechanistic line of investigation to prove that R-flurbiprofen (the R-enantiomer of the NSAID flurbiprofen, E-7869) has anti-cancer properties , and possibly anti-Alzheimer’s Disease activity as well. R-flurbiprofen does not significantly inhibit the cyclooxygenase enzymes, COX-1 or 2, unlike the non-selective NSAIDs aspirin and ibuprofen. Early EncorePharma Laboratory studies showed that one of the modes of action is modulation of the signal transduction and transcription pathway associated with nuclear factor kappa B (NFkB), a principle transcription factor in the expression of many molecules that mediate cell growth/death and inflammation. In animal models of cancer, EncorePharma Laboratory scientists have demonstrated R-flurbiprofen’s significant anti-tumor and anti-metastatic activity. They reported that R-flurbiprofen essentially cures Min mice of intestinal tumors (adenomas) and significantly reduced the incidence of primary and secondary prostate tumors  in the TRAMP model.

Subsequently, through a series of pioneering preclinical/clinical study designs, professionals at EncorePharma accomplished a bio-bridge to previous animal toxicology and human-use data on R-flurbiprofen  when given as part of a racemate. This approach is expected to reduce time to commercialization by several years as compared to the typical time frame for development of new chemical/biological entities.

*Patent-protected compound or uses