Reconciling Selectivity Trends from a Comprehensive Kinase Inhibitor Profiling Campaign with Known Activity Data

ACS Omega
Filip Miljković, Jürgen Bajorath

Abstract

Kinase inhibitors are among the most intensely investigated compounds in medicinal chemistry and drug development. Profiling experiments and kinome screens reveal binding characteristics of kinase inhibitors and lead to better understanding of selectivity and promiscuity patterns. However, only limited amounts of profiling data are publicly available. By contrast, a large body of activity data for inhibitors of human kinases has become available from medicinal chemistry. In this study, we have correlated selectivity assessment of clinical kinase inhibitors from the most comprehensive profiling campaign reported to date with systematic mining of activity data from other sources. The results of our comparative analysis reveal consistency of orthogonal approaches in the study of kinase inhibitor selectivity versus promiscuity and stress the importance of taking alternative data confidence criteria into account. Moreover, it is also shown that there are little if any detectable differences in selectivity between type I and II kinase inhibitors and that inhibitors designated as chemical probes have very different target profiles.

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Sep 18, 2018·ACS Omega·Filip Miljković, Jürgen Bajorath

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Citations

Sep 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Filip Miljković, Jürgen Bajorath
Dec 4, 2019·Journal of Computer-aided Molecular Design·Filip Miljković, Jürgen Bajorath
Mar 31, 2018·Molecular Informatics·Filip Miljković, Jürgen Bajorath
Mar 28, 2019·Journal of Computer-aided Molecular Design·Filip MiljkovićJürgen Bajorath
Jun 4, 2021·Bioorganic & Medicinal Chemistry·Huabin Hu, Jürgen Bajorath

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Methods Mentioned

BETA
proteomics profiling

Software Mentioned

CATDS
ChEMBL

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