What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases.


:Leukotrienes have physiological roles in innate immune responses and pathological roles in inflammatory diseases, such as asthma, allergic rhinitis and atherosclerosis. Anti-leukotriene therapy has proven benefits in the treatment of respiratory disease, either through the inhibition of leukotriene synthesis or the selective antagonism of leukotriene receptors. The first committed step in the synthesis of leukotrienes is the oxidation of arachidonic acid (AA) by 5-lipoxygenase (5-LO), and the integral membrane protein 5-lipoxygenase-activating protein (FLAP) is an essential partner of 5-LO for this process. FLAP was molecularly identified via a photoaffinity probe and an affinity gel based on MK-886, a selective leukotriene inhibitor that has no activity against broken-cell preparations of 5-LO. Several FLAP inhibitors showed efficacy in early clinical trials in asthma but were not developed commercially for unpublished reasons. Recently, the FLAP (ALOX5AP) gene has been linked to risk for myocardial infarction, stroke and restenosis, reigniting pharmaceutical interest in this target. In addition, the recent determination of the crystal structure of inhibitor-bound FLAP offers exciting potential for novel FLAP inhibitor design.


Trends Pharmacol Sci


Evans JF,Ferguson AD,Mosley RT,Hutchinson JH




Has Abstract


2008-02-01 00:00:00














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    authors: Konopatskaya O,Poole AW

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  • The schizophrenic faces of PICK1.

    abstract::Schizophrenia is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-k...

    journal_title:Trends in pharmacological sciences

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    authors: Dev KK,Henley JM

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    authors: Lechleiter J,Peralta E,Clapham D

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  • Discoidin Domains as Emerging Therapeutic Targets.

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    journal_title:Trends in pharmacological sciences

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    authors: Tang T,Gong T,Jiang W,Zhou R

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    pub_type: 杂志文章,评审


    authors: Inestrosa NC,Perelman A

    更新日期:1989-08-01 00:00:00

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  • Drug-lipid interaction evaluation: why a 19th century solution?

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    authors: Filtz TM,Vogel WK,Leid M

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hen R

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  • Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling.

    abstract::Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A ph...

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    authors: Guidotti A,Dong E,Kundakovic M,Satta R,Grayson DR,Costa E

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  • A Coordinated Attack: Rett Syndrome Therapeutic Development.

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    journal_title:Trends in pharmacological sciences

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    pub_type: 杂志文章,评审


    authors: Ward WH,Timms D,Fersht AR

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  • Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors.

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    pub_type: 杂志文章,评审


    authors: Drouin-Ouellet J,Cicchetti F

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    authors: Kotturi MF,Hunt SV,Jefferies WA

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: van Hooft JA,Yakel JL

    更新日期:2003-04-01 00:00:00

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Szabo G,Otero AS

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Mayer ML,Miller RJ

    更新日期:1990-06-01 00:00:00

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Buisson B,Bertrand D

    更新日期:2002-03-01 00:00:00

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Kobilka BK

    更新日期:2011-04-01 00:00:00

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Larsen BT,Campbell WB,Gutterman DD

    更新日期:2007-01-01 00:00:00

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    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hartig PR

    更新日期:1989-02-01 00:00:00