R-flurbiprofen

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R-flurbiprofen is the single enantiomer of the racemate NSAID flurbiprofen. This compound is currently in clinical trials for the treatment of metastatic prostate cancer, and Alzheimer's disease. At therapeutic concentrations, this molecule lacks anti-inflammatory activity, and does not inhibit either cyclooxygenase 1 or cyclooxygenase 2 (COX) enzymes. Only the S-enantiomers of arylpropionic acid NSAIDS can potently inhibit COX, whereas the R-enantiomers exert almost no COX activity. R-flurbiprofen is inefficiently converted into S-flurbiprofen, with 1.5% of the R-enantiomer undergoing bioinversion to the S-form.

Although this compound lacks activity against COX, studies have shown that this drug [1][2] is a potent reducer of levels of Beta amyloid, the main constituent of amyloid plaques in Alzheimer's disease, and therefore there was interest in this drug as a therapeutic agent. Myriad Genetics is running the largest ever Alzheimer's drug treatment trial using R-flurbiprofen [3]. The company is conducting a Phase III clinical trial with R-flurbiprofen (Flurizan™, MPC-7869) in order to determine if this compound can slow the progression of Alzheimer's disease [4]. A Phase II clinical trial in 207 subjects with mild to moderate AD was completed in 2006. Patients were split into three treatment groups, receiving placebo, 400 or 800 mg R-flurbiprofen twice daily for a year. Result from this trial showed that the drug was well tolerated, and positive trends were observed with the 800 mg twice-daily dose in patients with mild Alzheimer's disease. A subgroup of patients that were diagnosed with mild disease, and had high plasma drug levels, showed significantly less decline in 2 primary behavioral outcomes (Activities of Daily Living scale (ADCS-ADL) and Global Function (CDR-SB)). Patients enrolled in an optional follow-on study showed continuing benefits with R-flurbiprofen, with increasing positive trends over this period for all primary outcomes after 18 months. The ongoing Phase III clinical study is evaluating 800 mg R-flurbiprofen twice daily versus placebo for 18 months exclusively in patients with mild Alzheimer's disease; this trial is scheduled to conclude in 2007.