1005828 合理的創薬は可能か？
Molecular-based drug discovery
↓
Structure-based drug design (one drug, one target)
↓
Database-used in silico screening (one drug, all target)??
●Molecular-based drug discovery
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Nature 1990 vol 347, pp645
Ligand binding and co-activator assembly of the peroxisome prolifertor-activated receptor-gamma
Nature 1998, vol 397, pp137
●Structure-based drug design (one drug, one target)
立体構造をもとにSelectivityを高めることQ-SAR戦略。
しかし、Lead compoundによる制約。
→ 化合物ライブラリーからLead compoundをスクリーニング。
Flagment-based drug discovery, FBDD
Q-SAR + FBDD しかし、ほとんどがphase I
副作用が問題
●Database-used in silico screening (one drug, all target)??
Predicting new molecular targets for known drugs
Nature (2009),462,pp175
Comprehensive Structural Classification of Ligand-Binding Motifs in Proteins
Structure (2009), 17, pp234
Q-SAR + FBDD => Higher selectivity
↓
Database screening => Lower side-effect