Protein kinases continue to hold tremendous promise for therapeutic intervention, and the search for novel, safe and efficacious kinase inhibitors has intensified over the past decade. Given that most kinases are readily inhibited by organic small molecules and that a wealth of structural data exists on kinase-inhibitor complexes, there has been almost universal success in the design and identification of potent kinase inhibitors. The issues of non-selectivity and congested IP space, however, present formidable challenges for the successful clinical development of these compounds. We describe a systematic approach implemented at Abbott to enable the rapid discovery and design of novel and potent kinase inhibitors that provide additional opportunities for targeting new intellectual property space and achieving acceptable selectivity profiles.