Analysis of Kinase Inhibitor Selectivity using a Thermodynamics-Based Partition Index

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• 作者：Alan C. Cheng ; John Eksterowicz ; Stephanie Geuns-Meyer ; Yaxiong Sun
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：June 10, 2010
• 年：2010
• 卷：53
• 期：11
• 页码：4502-4510
• 全文大小：1081K
• 年卷期：v.53,no.11(June 10, 2010)
• ISSN：1520-4804

文摘

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.