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Mutations in a Molecule: The Virtues of Antagonism

Drug development has evolved through eras of natural product use (willow bark, which contains aspirin), serendipitous discovery (penicillin from bread mold), more rational drug design that involves the testing of diverse synthetic analogues and structural refinement after identification of endogenous ligands (leading to development of β-adrenergic blockers), and fortuitous drug discovery (sulfanilamide that evolved to the sulfonylurea antibiotics and to loop diuretics).1 High (and progressively higher)-through-put screening (a practical method using miniaturized assays to evaluate large numbers of structurally diverse compounds for pharmacological activity) evolved to screen large ...

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