Tarenflurbil, Flurizan or ''R''-flurbiprofen, is the single

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

of the

racemate In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

flurbiprofen Flurbiprofen is a member of the phenylalkanoic acid derivative family of nonsteroidal anti-inflammatory drugs (NSAIDs). It is primarily indicated as a pre-operative anti-miotic (in an ophthalmic solution) as well as orally for arthritis or dent ...

. For several years, research and trials for the drug were conducted by

Myriad Genetics Myriad Genetics, Inc. is an American genetic testing and precision medicine company based in Salt Lake City, Utah, United States. Myriad employs a number of proprietary technologies that permit doctors and patients to understand the genetic bas ...

, to investigate its potential as a treatment for

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

; that investigation concluded in June 2008 when the company announced it would discontinue development of the compound.Myriad Genetics Reports Results of U.S. Phase 3 Trial of Flurizan in Alzheimer's Disease
from the

website.

Mechanism of action

At proposed therapeutic concentrations, this molecule lacks anti-inflammatory activity, and does not inhibit either

cyclooxygenase 1 Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prosta ...

(COX-1) or

cyclooxygenase 2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...

(COX-2) enzymes. Only the ''S''-enantiomers of arylpropionic acid

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 Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labio ...

, the main constituent of

amyloid Amyloids are aggregates of proteins characterised by a Fibril, fibrillar morphology of 7–13 Nanometer, nm in diameter, a beta sheet (β-sheet) Secondary structure of proteins, secondary structure (known as cross-β) and ability to be Staining, ...

plaques in

, and therefore there was interest in this drug as a therapeutic agent.

Clinical trials

In 2005,

reported the results of its

Phase II clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

of Flurizan; it was the largest ever Alzheimer's drug treatment trial using ''R''-flurbiprofen. 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 two 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 those 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. A Phase III clinical study evaluated 800 mg ''R''-flurbiprofen twice-daily versus placebo for 18 months exclusively in 1800 patients with mild Alzheimer's disease. This second trial concluded in February 2008 with results reported in the summer. After Phase III testing, which included nearly 1,700 patients with mild Alzheimer’s disease treated for 18 months with either Flurizan or placebo, Myrial Genetics concluded that the drug did not improve thinking ability or the ability of patients to carry out daily activities significantly more than those patients with placebo. Peter Meldrum, the chief executive of Myriad, announced on June 30, 2008, that the company will no longer be developing Flurizan. Prior to this termination, Myriad had sold distribution rights in the European Union to

Lundbeck H. Lundbeck A/S (commonly known simply as Lundbeck) is a Danish international pharmaceutical company engaged in the research, development, manufacturing, marketing and sale of pharmaceuticals across the world. The company’s products are target ...

for an initial payment of $100 million, which Lundbeck has indicated it will now take as a

write-down A write-off is a reduction of the recognized value of something. In accounting, this is a recognition of the reduced or zero value of an asset. In income tax statements, this is a reduction of taxable income, as a recognition of certain expenses ...

References

External links

* {{Prostanoidergics Nonsteroidal anti-inflammatory drugs Fluoroarenes Biphenyls Enantiopure drugs