PhoreMost Ltd, a next-generation targeted protein degradation (TPD) company advancing a pipeline of degrader therapeutics in oncology and inflammation, announces the publication of a study demonstrating the capabilities of its high-throughput GlueSEEKER platform to accelerate the design and development of novel molecular glue degraders.
The paper, titled “Systematic Molecular Glue Drug Discovery with a High-Throughput Effector Protein Remodeling Platform,” was published in BioRxiv and describes PhoreMost’s unique approach to molecular glue discovery, wherein effector proteins, such as E3 ligases, can be engineered at scale to expand protein surface landscapes and trigger induced degradation of target proteins.
GlueSEEKER is used to develop a high-resolution understanding of the physical and chemical requirements for molecular glue development, providing the blueprints to enable small-molecule drug discovery.
The approach synthesises quantitative high-throughput biological data with the most recent advances in computational small molecule drug discovery.
The study provides a detailed description of PhoreMost’s GlueSEEKER and documents an end-to-end case study for small molecule molecular glue discovery using the technology.
The potential of the platform to accelerate programmes is validated by the published data and methodology, which can also be applied to novel E3 ligases and other effector proteins across broad therapeutic areas.
Dr Benedict Cross (pictured left), CTO, PhoreMost, said: “Molecular glues have now been established as an effective therapeutic modality, but these small molecule drugs have still largely only been found through serendipity."
"Our GlueSEEKER platform overcomes the challenges associated with monovalent glue discovery, enabling its rational and systematic design from almost any E3 ligase or target."
"This paper marks a significant milestone by showcasing one of our case studies and validating our deep mutational scanning approach for prospective drug discovery.”
Dr Neil Torbett (pictured right), CEO, PhoreMost, commented: “FDA-approved molecular glues have treated millions of patients and generated billions of dollars in revenue."
"The advances disclosed within this manuscript demonstrate how GlueSEEKER can radically enable the discovery of new molecular glue therapies, directing this modality towards specific targets across a broad array of E3 ligases.”