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We analyzed the target enzymes of drugs containing new active ingredients (NAIs) focusing on the characteristics of the reaction of the enzymes, and attempted to prepare a comprehensive overview of the changes in the approval of the drugs over a 3 decade period from 1980 to 2009 in Japan. Fifty-eight enzyme therapeutic targets of 235 NAIs were found to be primarily distributed to EC1, EC2 and EC3 classes, and the enzymes were unevenly distributed to 21 of 64 sub-classes and 34 of 264 sub-subclasses, respectively, classified by the enzyme nomenclature of the International Union of Biochemistry and Molecular Biology (IUBMB). Though the number of NAIs approved that targeted EC1 class enzymes decreased over the time frame studied, the number of NAIs which targeted EC2 class enzymes increased over the same time. There was no clear change in the number of NAIs which targeted other classes of enzymes. More than 80% of NAIs targeted one enzyme as a primary target, and less than 20% of NAIs targeted more than two enzymes as secondary targets. NAIs which primarily targeted EC2 and EC3 class enzymes had more secondary target enzymes than other classes. The results of this study revealed the characteristics of the reactions of the target enzymes of NAIs and the changes in NAI approvals in Japan during the three decades studied, and provided information regarding possible future trends of NAIs.

yakugaku zasshi

Characteristics of Reactions of Target Enzymes of Drugs Containing New Active Ingredients (NAIs) and Changes of the NAIs Approvals over Three Decades from 1980 to 2009 in Japan