PhoreMost introduces GlueSEEKER platform for discovery of molecular glue degraders
May 21, 2024 – Biotechnology, Drug Discovery, Pharmaceutical – Phoremost, molecular glue degraders, phenotypic screening platform
New drug discovery platform integrates computational approaches with molecular biology for development of novel degrader therapeutics
21 May 2024 — Cambridge, UK — PhoreMost, a leading UK biopharmaceutical company unlocking the next generation of drug targets, today announced the introduction of GlueSEEKER. The new phenotypic screening platform expands the company’s capabilities in this emerging therapeutic modality to support the systematic discovery and development of novel molecular glue degraders (MGDs) for targeted protein degradation (TPD).
MGDs are an important new class of small molecule drug that exhibit a therapeutic effect by enhancing the affinity between proteins, inducing new interactions or stabilising a molecular complex. Similar to bivalent degraders like PROTACs, MGDs induce close proximity between target and effector proteins and are able to exploit the cell’s proteostasis mechanisms to cause target degradation. This approach has great potential in the treatment of diseases from cancer to neurodegeneration and beyond.
PhoreMost has developed the GlueSEEKER platform to overcome the challenges in discovering this class of molecule and provide a systematic discovery approach to address undruggable or otherwise unaddressed therapeutic targets. Expanding on the company’s established SITESEEKER degrader discovery platform, GlueSEEKER uses computationally designed intramolecular libraries to create a vast diversity of surface-edited E3 ligases. Phenotypic screening is then deployed to identify specific sites and precise changes resulting in induced degradation activity, integrating deep computational approaches with novel biological discovery.
The new GlueSEEKER platform has broad-ranging applications and is able to identify induced degradation events for almost any nominated neosubstrate and ligase pair, expanding the scope for this important modality and providing the company and its partners with opportunities for novel therapeutic pipeline development. The technology innovation expands the company’s activities in TPD and complements a growing internal pipeline of novel ligase-based bivalent degraders as they progress to development candidates.
Dr Benedict Cross, chief technology officer, PhoreMost, said: “GlueSEEKER builds on our expertise in the TPD space, offering an innovative solution to the rational discovery of new MGDs and for molecular glues beyond the degradation modality. This unique and powerful approach is a substantial augmentation of our existing platform technologies, providing new opportunities to unlock MGDs to help us and our partners to bring new precision medicines to fruition faster.”
About PhoreMost
Powered by its proprietary SITESEEKER technology, PhoreMost is developing a pipeline of novel E3-ligase based ‘next-generation’ degrader therapeutics. Targeted Protein Degradation (TPD) is a promising new way to eliminate toxic or disease-associated targets from cells, with degradation-based therapies now becoming an integral approach to tackling undruggable targets. However, despite there being over 600 known E3 ligases, the pharma industry is currently reliant upon a very small number, such as Cereblon, for degrader-based drug development. Harnessing the SITESEEKER platform, PhoreMost is progressing a portfolio of novel degrader programmes specifically tailored to identify functionally active binding sites on novel E3 ligases in oncology and inflammatory diseases. This unique ‘function-first’ approach provides the company with the ability to unlock TPD’s full potential, enabling the discovery and progression of E3 ligases with both target-specific and tissue-selective activities. PhoreMost also has a number of disclosed alliances with partners, including: Roche, Otsuka, Boehringer Ingelheim and Sentinel Oncology. www.phoremost.com
