Date

Thursday 01 Oct 2026

Time

15:15 - 15:45

Location

BW029

Supervisor

Mario van der Stelt

2nd reviewer

Anthe Janssen

Jury

Bobby Florea

Kinases serve as pivotal regulators of cellular signal transduction pathways, with dysregulation implicated in major pathologies such as cancer, cardiovascular disease, immunological disorders, and neurodegeneration. Currently there are more than 100 FDA-approved kinase inhibitors. However these cover less than 10% of the kinome. The huge potential to develop first in class kinase inhibitors requires tools to study target engagement beyond well understood kinases. This can be achieved using broad-spectrum kinase probes in the chemical proteomics platform CellEKT. To further optimize the current set of chemical probes towards probes with increased metabolic stability that can be used to study in vivo target engagement. In this thesis salicylic aldehyde and ethynylbenzaldehyde OTS-167 derivatives were designed and synthesized. Their protein labelling was investigated by SDS PAGE. Future proteomics experiments will further determine exact kinome coverage and in vitro studies whether the probes 1-10 show increase metabolic stability compared to prior probes.