IngentaConnect R-Flurbiprofen (E-7869), a chemopreventive and treatment of cance...

Authors: Wechter, W.J.; Leipold, D.D.; Quiggle, D.D.; McCracken, J.D.; Murray Jr., E.D.; Loughman, B.E.

Source: Inflammopharmacology, Volume 8, Number 2, 2000 , pp. 189-206(18)

Abstract:

R-flurbiprofen, the non-COX inhibiting enantiomer of the non-steroidal antiinflammatory (NSAI) agent R-, S-flurbiprofen has proved to have a pharmacology independent of the S-enantiomer. In this presentation, we recount its anti-proliferative activity in the rat in addition to its anti-cancer activity without significant ulcerogenicity in the Min and TRAMP mouse models. In the Min mouse (a model of human FAP) R-flurbiprofen proved 'curative'. It had significant activity against both the primary lesion in the TRAMP mouse (a model of prostate cancer) and metastatic disease which was influenced by the amount of saturated fat in the diet.

Surprisingly, we found R-flurbiprofen anti-inflammatory in the rat hind-paw edema assay. From our accumulating data, and the work of others, R-flurbiprofen has pro-apoptotic activity. We hypothesize that the mechanism of R-flurbiprofen's pro-apoptotic activity is inhibition of COX-2 m-RNA transcription and/or down-regulation of NF_kB. We believe that R-flurbiprofen will delay or prevent progression of epithelial pre-malignant lesions to carcinoma (colon, prostate, lung and breast) without significant side effects. In addition, as hypothesized for other modifiers of cyclo-oxygenase activity, it may delay or prevent progression of Alzheimer's Disease. Phase I and IIa clinical studies with oral R-flurbiprofen (E-7869) have begun in normal volunteers and prostate cancer patients.

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R-Flurbiprofen (E-7869), a chemopreventive and treatment of cancer