AI Article Synopsis
- Triazolo[4,5-d]pyrimidin-5-amines are identified as new ERK3 inhibitors that work effectively at concentrations below 100 nanomolar in lab tests.
- Their binding mode was characterized using ERK3 crystal structures, showing how they affect critical loops and helices in the ATP pocket, which could enhance MK5 interactions.
- These inhibitors demonstrated strong performance in both biochemical assays and a cellular ERK3 NanoBRET assay, paving the way for further research on ERK3's biological roles and activation processes.
Article Abstract
Triazolo[4,5-d]pyrimidin-5-amines were identified from kinase selectivity screening as novel ERK3 inhibitors with sub-100 nanomolar potencies in a biochemical assay using MK5 as substrate and with an attractive kinase selectivity profile. ERK3 crystal structures clarified the inhibitor binding mode in the ATP pocket with impact on A-loop, GC-loop and αC-helix conformations suggesting a potential structural link towards MK5 interaction via the FHIEDE motif. The inhibitors also showed sub-100 nM potencies in a cellular ERK3 NanoBRET assay and with excellent correlation to the biochemical ICs. This novel series provides valuable tool compounds to further investigate the biological function and activation mechanism of ERK3.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2020.127551 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!