Now showing items 1-5 of 5
Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766).
Demonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging ...
A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.
The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority ...
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.
HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought ...
The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.
The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we ...
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.
The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 ...