Tarenflurbil
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Tarenflurbil
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| Systematic (IUPAC) name | |
| (2R)-2-(3-Fluoro-4-phenylphenyl)propanoic acid | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C15H13FO2 |
| Mol. mass | 244.26 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
Tarenflurbil, or R-flurbiprofen, is the single enantiomer of the racemate NSAID flurbiprofen. This compound is currently in clinical trials for the treatment of Alzheimer's disease, and has been assigned the generic name tarenflurbil.[1] At therapeutic concentrations, this molecule lacks anti-inflammatory activity, and does not inhibit either cyclooxygenase 1 (COX-1) or cyclooxygenase 2 (COX-2) 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 is a potent reducer of levels of beta amyloid,[2][3] the main constituent of amyloid plaques in Alzheimer's disease, and therefore there was interest in this drug as a therapeutic agent.
[edit] Clinical trials
Myriad Genetics is running the largest ever Alzheimer's drug treatment trial using R-flurbiprofen.[4] 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.[5] 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 had significantly less decline in 2 primary behavioral outcomes (Activities of Daily Living scale (ADCS-ADL) and Global Function (CDR-SB)). Approximately 80 patients enrolled in the optional follow-on study showed continuing benefits with R-flurbiprofen, with increasing positive trends over this period for all primary outcomes after 24 months. On March 5, 2007 Myriad reported final results of the two-year trial, showing that 42% of approximately 80 patients showed improvement or no decline in one or more of the three primary endpoints of cognition, global function and activities of daily living, compared to a typical 10% of patients on placebo. Although this patient data is impressive and suggests that this drug may slow or halt progression of mild Alzheimer's disease, this results will require replication in a larger patient population.The ongoing Phase III clinical study is evaluating 800 mg R-flurbiprofen twice daily versus placebo for 18 months exclusively in 1800 patients with mild Alzheimer's disease. This trial is scheduled to conclude in February 2008 with results reported in the summer.
[edit] References
- ^ www.myriad.com Update on Flurizan
- ^ www.pubmedcentral.gov NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
- ^ www.ncbi.nlm.nih.gov Selective inhibition of Abeta42 production by NSAID R-enantiomers
- ^ www.usatoday.com Biotech launches largest-ever Alzheimer's drug trial
- ^ www.myriad.com FLURIZAN & Alzheimer's Disease
