Charnwood Molecular’s bioscience team believe in the power of communicating their research and sharing insights gained.
Posters are ideal for conveying research and areas of expertise in a visually engaging yet informative format.
The bioscience team regularly create posters for presentation at conferences and events, in addition to sharing them internally with colleagues.
Take a look at our latest posters.
Beyond Degradation: Cell-based and Biophysical PROTAC Characterisation
In the development of PROTACs it is vital to have a varied suite of assays that can inform the structure-activity relationship (SAR) and progress the design-make-test cycle. A number of PROTACs have previously been developed to target the well-studied protein BRD4 – a member of the BET (bromodomain and extra-terminal) family of proteins whose dysregulation is linked to human cancers. At Charnwood Molecular we have used cell-based and biophysical techniques to investigate – amongst others – the BRD4-targeting PROTAC ‘dBET6’ to elucidate a binding mechanism, confirm proteasomal degradation and monitor its impact on cellular behaviour. Here we demonstrate the techniques that we might typically implement in a PROTAC development cascade.
Investigating 3D Tumour Spheroids and Immune Cell Models
Cell-based assays are an essential component of many drug discovery programs and the ability to monitor how cells react to novel compounds in real time is invaluable.
At Charnwood Molecular we use the IncuCyte® SX5 for all our real-time live-cell imaging needs. This instrument allows us to investigate cell behaviour in a kinetic manner for extended time periods, from simple confluency monitoring to experiments including multiple cell dyes and labels.
This capability is essential when developing cell-based assays and when screening compounds in in vitro culture to fully understand how cells behave and add value to client projects.
Using SPR to Characterise the Binding Modes of PROTAC Molecules
PROteolysis-TArgeting Chimeras (PROTACs) are an exciting new development in drug discovery that have the potential to modulate protein targets once considered ‘undruggable’.
A small molecule is designed with two “warheads”, one binds to the protein target of interest (TOI) and the second binds to an E3 ligase such as VHL (right). The two are joined by a flexible linker which allows the E3 ligase to ubiquitinate the TOI – targeting it for degradation by the intracellular ubiquitin proteasome system.
Using SPR to Drive Integrated Screening Projects
An existing client was interested in an additional, integrated project with Charnwood Molecular to learn more about their lead compound. In collaboration with a third-party external computational chemist our chemistry department arranged a virtual screen of tens of thousands of compounds against their lead compound’s protein target.
From the list of docking hits a set of ~ 100 compounds was identified that would help confirm our ideas about the binding mode of the lead compound and improve our confidence in the model that had been generated for future docking work. This set was purchased and brought in-house.
Protein Detection Capabilities
Accurate determination of protein quantity and monitoring of signalling pathways within a cell background is a powerful tool to further understand mechanisms of action within the drug discovery field.
Western blotting has been the gold standard method for detection of protein within biological samples for decades, however, this method is time consuming, suffers from poor reproducibility, and only allows for the collection of qualitative data.
