title: Analysis of kinase inhibitor selectivity using a thermodynamics-based partition index.
abstract: In the quest for safe, efficacious kinase inhibitors as drugs, selectivity is often assessed early using kinase profiling panels. Here we present a selectivity index based on thermodynamics principles that can help in analysis of the resulting data. The "partition" selectivity index is easy to calculate and is applicable in certain situations where other widely used indices are not. It is uniquely useful in analysis of small, focused selectivity panel data frequently encountered in medicinal chemistry hit-to-lead and lead optimization. For larger "kinome" panels, the partition index allows assessment of selectivity relative to a kinase or multiple kinases of interest.
authors.affiliation: Molecular Structure Department, Amgen Inc., 360 Binney Street, Cambridge, Massachusetts 02142, USA. alan.cheng@amgen.com
authors.forename: Alan C
authors.initials: AC
authors.lastname: Cheng
authors.forename: John
authors.initials: J
authors.lastname: Eksterowicz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Geuns-Meyer
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Sun
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods*; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases