Abstract
Kinases represent one of the most intensively pursued groups of targets in modern-day drug discovery. Often it is desirable to achieve selective inhibition of the kinase of interest over the remaining ∼500 kinases in the human kinome. This is especially true when inhibitors are intended to be used to study the biology of the target of interest. We present a pipeline of open-source software that analyzes public domain data to repurpose compounds that have been used in previous kinase inhibitor development projects. We define the dual-specificity tyrosine-regulated kinase 1A (DYRK1A) as the kinase of interest, and by addition of a single methyl group to the chosen starting point we remove glycogen synthase kinase β (GSK3β) and cyclin-dependent kinase (CDK) inhibition. Thus, in an efficient manner we repurpose a GSK3β/CDK chemotype to deliver 8b, a highly selective DYRK1A inhibitor.
Original language | English |
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Pages (from-to) | 1620-1626 |
Number of pages | 7 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 11 |
Issue number | 8 |
Early online date | 30 Jun 2020 |
DOIs | |
Publication status | Published - 13 Aug 2020 |
Keywords
- DYRK1A
- polypharmacology
- chemoinformatics
- selectivity
ASJC Scopus subject areas
- Drug Discovery
- Biochemistry
- Organic Chemistry