Several interesting innovation projects have resulted from the exploration of alternative kinase inhibition modes. Expert in-house knowledge and an efficient platform for development with our partners led to the following projects:
Potent CDK8 inhibitors with long residence times
Mercachem and ProQinase developed proprietary scaffolds with a pre-engineered binding kinetics signature. Excellent in vitro activity and cell-based efficacy in the nanomolar range was found for inhibitors with long residence times (>7 h).
CK1d inhibitors with pharmacokinetic data in the CNS range
NBHealth Laboratory and Mercachem have designed interesting inhibitors for this enzyme, which plays a role in the mammalian circadian rhythm. Proprietary scaffold design and multiparameter optimization performed by iterative analogue library synthesis were performed. In vivo proof of concept was shown in animal studies.
PERK inhibitors to target unfolded protein response in brain tissue
Mercachem and the Neuroscience Campus Amsterdam have engaged in the design of deep-pocket binding inhibitors for PERK. The project is in the hit-to-lead stage with new proprietary scaffolds.