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Current compound coverage of the kinome.

Publicly available kinase inhibitors have been analyzed in detail. Nearly 19000 inhibitors have been identified with activity against 266 different kinases. Thus, about half of the human kinome is currently covered with active small molecules. The distribution of inhibitors across the kinome is uneven. Most available kinase inhibitors are likely to be type I inhibitors. By contrast, type II inhibitors are rare but usually have high potency. Kinase inhibitors generally display high scaffold diversity. Activity cliffs with an at least 100-fold difference in potency are only found for inhibitors of 106 kinases, which is partly due to only small numbers of compounds available for many kinases, in addition to scaffold diversity. Moreover, kinase inhibitors are less promiscuous than often thought. More than 70% of available inhibitors are only annotated with a single kinase activity, and only ∼1% of the inhibitors are active against five or more kinases.