Now showing items 1-6 of 6
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 ...
Privileged Structures and Polypharmacology within and between Protein Families.
Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (<b>1</b>) and the ...
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 a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.
Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug ...