Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.


:Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 nM in Chinese hamster ovary cells) assays. Inhibitor 24 has also shown very impressive in vivo properties (up to 65% reduction of plasma A beta) in transgenic mice. The X-ray structure of protein-ligand complex of memapsin 2 revealed critical interactions in the memapsin 2 active site.


Bioorg Med Chem Lett


Ghosh AK,Kumaragurubaran N,Hong L,Kulkarni S,Xu X,Miller HB,Reddy DS,Weerasena V,Turner R,Chang W,Koelsch G,Tang J




Has Abstract


2008-02-01 00:00:00














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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: McKnight RE,Reisenauer E,Pintado MV,Polasani SR,Dixon DW

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    更新日期:2013-04-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    更新日期:2015-11-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang SG,Kong LY,Li YH,Cheng XY,Su F,Tang S,Bi CW,Jiang JD,Li YH,Song DQ

    更新日期:2015-09-01 00:00:00