Kinase-targeted libraries: the design and synthesis of novel, potent, and selective kinase inhibitors.
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.
Akritopoulou-Zanze
Irini
I
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-3500, United States.
Hajduk
Philip J
PJ
D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D018973:Intellectual Property; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D054852:Small Molecule Libraries
D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D011494:Protein Kinases