Research towards selective inhibition of the CLK3 kinase  

Submitting author affiliation:
Institut des Sciences Chimiques de Rennes, CNRS UMR 6226 Avenue du Général Leclerc 35042 RENNES Cedex, Rennes, France

Beilstein Arch. 2025, 202544. https://doi.org/10.3762/bxiv.2025.44.v1

Published 04 Jul 2025

Preprint
cc-by Logo
This preprint has not been peer-reviewed. When a peer-reviewed version is available, this information will be updated.

Abstract

The cdc2-like kinases (CLKs), are a family of kinases that attracted recently the interest of scientists due to their significant biological roles, in particular in the regulation of mRNA splicing process. Among the four isoforms of CLKs, the CLK3 is the one for which the biological roles are less well understood, in part because no selective inhibitor of this challenging kinase has been found to date. Based on structural analysis of the CLKs we have identified the lysine 241, present only in CLK3, as an attractive target to design inhibitors with increased affinity towards this kinase as compared to the three others. Based on this, we have been able to transform a molecule (DB18) previously established with a low activity on CLK3 into a derivative (VS-77) which has now a significant affinity toward this CLK3 kinase (IC50 = 0.3mM). Further, since this compound has kept good activities against the other CLKs, VS-77 can be qualified as a new pan-inhibitor of the CLKs.

Keywords: Kinases • CLK3 • Quinazolines • Cancer • Triazoles • Molecular modelling

Supporting Information

Format: PDF Size: 1.6 MB   Download

How to Cite

When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

Singh, V. K.; Justaud, F.; Brahmaiah, D.; Kumar, N. S.; Baratte, B.; Robert, T.; Bach, S.; Reddy, C. R.; Levoin, N.; Grée, R. L. Beilstein Arch. 2025, 202544. doi:10.3762/bxiv.2025.44.v1

Download Citation

Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below.
Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Zotero.

OTHER BEILSTEIN-INSTITUT OPEN SCIENCE ACTIVITIES