The design, annotation, and application of a kinase-targeted library.
We present here a workflow for designing a kinase-targeted library (KTL) with the goal of capturing known kinase inhibitor chemical space. We validated our design retrospectively using recent, high-throughput screening data and found significant enrichment of kinase inhibitor hits while retaining majority of the active kinase inhibitor series. To further assist kinase projects in triaging KTL screen hits, we also developed a methodology to systematically annotate known kinase inhibitors in the KTL with regard to their binding modes.
Xi
Hualin
H
Pfizer Research Technology Center, Cambridge, MA, USA. hualin.xi@pfizer.com
Lunney
Elizabeth A
EA
D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D000255:Adenosine Triphosphate; D011494:Protein Kinases