Our Science
It is estimated that roughly 85% of disease targets are undruggable. Molecular glues are a new validated wave of medicines that render undruggable targets druggable.
Molecular glue degraders were serendipitously identified for their preferential cancer-cell killing properties. Later it was discovered that these drugs induce protein:protein interactions between disease targets and a component of the cell’s ubiquitin-proteasome system (UPS). Specifically, the mechanism involves E3 ligase enzymes, which tag target proteins with ubiquitin molecules to be recognized and degraded by the proteasome. This discovery prompted the search for other compounds that could promote degradation of disease targets by “gluing” them onto components of the cell’s UPS.
TRIANA is harnessing the full potential of molecular glues. Our approach is to start with challenging disease targets and leverage our proprietary protein:protein pairing engine to identify E3 ligases that are potential matches. We then initiate a comprehensive glue discovery campaign covering diverse chemical spaces to identify new molecular glues using a target-first and rational approach.
The most challenging disease-causing targets require a transformational approach, molecular glues
Molecular Glues – The best modality for targeted protein degradation: Molecular glue degraders eliminate disease-causing proteins by promoting their interaction with the cell’s UPS. Specifically, molecular glues have the potential to enhance binding between a disease-causing protein and an E3 ligase enzyme. These small molecules can effectively promote the formation of a complex between two proteins even with low binding affinity of the molecular glue to either protein partner. Molecular glues are a powerful tool for directing the UPS and their versatility allows us to effectively degrade undruggable targets.
TRIANA is industrializing molecular glue discovery
Target-first approach: We focus on addressing the root cause of diseases and select disease drivers not adequately drugged by traditional therapeutic approaches. We leverage genomic, functional and translational data to prioritize disease targets and candidate E3 ligases for molecular glue discovery.
Rational, prospective approach: Our platform technologies are uniquely designed to identify the preferred E3 ligases for a specific disease target and discover small molecules that directly promote the interaction of the disease target:E3 ligase pair.
Expanding druggable universe: Many well validated therapeutic targets are still escaping current drug modalities. We are developing a strong oncology pipeline by systematically selecting targets that can be best addressed by molecular glue degraders.
Powered by cutting-edge drug discovery technologies
Protein:protein pairing engine: We are using a multilayered approach, inclusive of artificial intelligence as well as experimental approaches to prioritize a short list of E3 Ligases out of the entire universe of greater than 600 E3 Ligases.
Bespoke molecular glue libraries: Molecular glues come in all shape and sizes. TRIANA explores a wide range of chemical spaces to discover novel molecular glues.
Customized approach to molecular glue identification: We are equipped to employ both biochemical and cell-based methodologies to uncover novel molecular glues.
TRIANA’s target-first and rational approach to molecular glue discovery is unlocking the full potential of small molecules to manipulate key disease drivers for therapeutic benefit.