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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/16497


    Title: A Novel Strategy for Designing the Selective PPAR Agonist by the “Sum of Activity” Model
    Authors: ;Huang, Hung-Jin;李桂仁;Lee, Kuei-Jen;Yu, Hsin Wei;Chen, Hsin-Yi;Tsai, Fuu-Jen;陳語謙;Chen, Calvin Yu-Chian
    Contributors: 生物科技學系
    Keywords: PPAR;Sum of activities;Obesity;QSAR.
    PPAR;Sum of activities;Obesity;QSAR.
    Date: 2010-10
    Issue Date: 2012-11-23 17:13:52 (UTC+8)
    Abstract: Peroxisome proliferator-activated receptors α, δ and γ are a collection of ligand-activated transcription factors crucial in lipid and glucose homeostasis. The involvement of these receptors in lipid metabolism makes them perfect therapeutic target for treating obesity and stroke. In this study, ‘sum of activity’ model was employed to design multi-target agonists. We used a new strategy to design agonists that fit both α and δ but not γ, to avoid side effect. The CoMFA and CoMSIA models were used to explore the pharmacophore features by constructing three individual models: (a) α-model, (b) δ-model and (c) &gammma;-model, and two sum models: (d) α, δ- model, and (e) α, δ and γ-model. The CoMFA model yielded a significant cross validation value, q2, of 0.729 and non-cross validation value, r2, of 0.933 in the α, δ-model. The CoMSIA studies yielded the best predictive models with q2 of 0.622 in A+S and with r2 of 0.911 in the α, δ-model. Finally, we proposed that distinct features shown in models (a), (b), (d) but not (c) and (e) should be accounted in designing weight-controlling drugs.
    Peroxisome proliferator-activated receptors α, δ and γ are a collection of ligand-activated transcription factors crucial in lipid and glucose homeostasis. The involvement of these receptors in lipid metabolism makes them perfect therapeutic target for treating obesity and stroke. In this study, ‘sum of activity’ model was employed to design multi-target agonists. We used a new strategy to design agonists that fit both α and δ but not γ, to avoid side effect. The CoMFA and CoMSIA models were used to explore the pharmacophore features by constructing three individual models: (a) α-model, (b) δ-model and (c) &gammma;-model, and two sum models: (d) α, δ- model, and (e) α, δ and γ-model. The CoMFA model yielded a significant cross validation value, q2, of 0.729 and non-cross validation value, r2, of 0.933 in the α, δ-model. The CoMSIA studies yielded the best predictive models with q2 of 0.622 in A+S and with r2 of 0.911 in the α, δ-model. Finally, we proposed that distinct features shown in models (a), (b), (d) but not (c) and (e) should be accounted in designing weight-controlling drugs.
    Relation: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
    Appears in Collections:[生物科技學系] 期刊論文

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