Most drugs are designed to inhibit or activate the function of specific proteins. However, many disease-related proteins cannot be targeted in this way and are therefore considered ‘undruggable’. As an alternative to conventional inhibitors or activators, molecular glues are emerging as a promising therapeutic modality. These small molecules either promote de novo interactions between disease-relevant proteins and other proteins or stabilize native interactions, thereby altering protein function. Molecular glues offer new opportunities to render previously undruggable targets druggable, while potentially reducing the toxicity associated with traditional inhibitors or protein degraders.

As part of the Symeres group, Oncolines can support clients with the synthesis, optimization and development of molecular glues, complemented by state-of-the-art biophysical and functional validation studies. This includes our surface plasmon resonance platform ResidenceTimer™ for evaluation of binary and ternary complex formation. Moreover, our Mechanistic Cell Biology services can aid the understanding or validation of mechanisms of action through use of different technologies, whereas our Oncolines cancer cell panel proliferation platform allows for broad screening and the identification of drug response biomarkers. Together, these services aim to advance pre-clinical research towards clinical development.

Oncolines has recently started a collaboration with Ambagon Therapeutics to investigate their newly designed molecular glues in the context of colorectal cancer. In this project, the formation of ternary complexes comprising disease-relevant proteins, intended binding partners and molecular glues will be thoroughly investigated using surface plasmon resonance (ResidenceTimer™). Using fluorescence microscopy, the effect of the molecular glues on blockade of target protein nuclear translocation, and thus inhibition of the relevant pathway will be evaluated in cellular models. Furthermore, changes in RNA and protein levels of pathway components will be monitored using qPCR and Western blot analysis, and the in vitro effect of the molecular glues on cancer cells will be assessed using viability assays. By combining Ambagon’s molecular glue technology with our translational research capabilities, we aim to generate meaningful insights to accelerate preclinical development across a variety of therapeutic conditions.