By Meijer, D. K. F.; Molema, Grietje
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Additional resources for Drug targeting : organ-specific strategies
These few examples were chosen to illustrate different elements of convergence that can be exploited to utilize suggestive pharmacophore relations for crossfertilizing medicinal chemistry projects on targets in the same or different protein families. 15 Co-substrate similarity between ATP (top left) and PAPS (top right) initiated a directed search for carbohydrate sulfo-transferase inhibitors based on kinase inhibitor compound collections [67, 68, 72]. The resulting sulfotransferase inhibitors together with their inhibitory activities are shown at the bottom.
The concept of ‘fewer of many’ as opposed to ‘many of fewer’ offers a substantially increased likelihood of discovering viable lead compounds . The current disillusion with screening huge, diverse libraries [20–23] has led to the tendency to screen libraries that are biased toward our current medicinal chemistry know-how [24, 25]. This reflects both the nonuniform distribution of drugs in chemistry space and the realization that ADMET properties are as relevant as, or even more relevant than, pure target affinities in the search for candidate compounds with realistic therapeutic potential [16, 26, 27].
Brand name Ingredient Company Indication targets Sales (growth) [$ million] Nexium® Esomeprazole AstraZenec ulcers proton pump inhibitor 623 (999%) Protonix® Pantoprazole Altana/Wyeth ulcers proton pump inhibitor 695 (426%) Advair® Albuterol & Fluticasone GlaxoSmithKline β2 agonist & corticosteroid asthma 1103 (351%) Remicade® Infliximab J&J/Schering-Pl. 5 billion in 2001, thus claiming a market share of 6%. 9 billion). 7 billion. It is interesting to note that four classes grew more than 20% in 2001, namely the cholesterol reducers (22%), the antipsychotics (30%), the oral antidiabetics (30%), and the antihistamines (22%) .