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Covalent screening has become a powerful strategy in modern small-molecule drug discovery, enabling researchers to tackle targets that are often difficult to address using traditional approaches. Once viewed as high risk, covalent strategies are now widely recognized for their ability to deliver potent, selective, and long-lasting therapeutics.
Unlike conventional screening methods, covalent approaches rely on more than transient binding interactions. They require a carefully tuned balance between reversible target recognition and covalent bond…
How Screening Covalent Libraries Lands Hits Where Others Fail?
As part of our mission to tackle some of the toughest targets in drug discovery, we’ve recently expanded our early discovery capabilities to include covalent compound library screening. Our early discovery site in Leiden is already well-known for its success in first-in-class and hard-to-drug targets, and this addition reflects a growing shift in the field: covalent approaches are no longer a last resort, they are becoming a smart, mechanism-led starting point for small molecule discovery. To understand what makes covalent screening so powerful…
A Q&A with Molecular Glue Hunter Pim de Vink on the current challenges and opportunities in this rapidly evolving field of research
Molecular glues are redefining how we approach drug discovery, enabling the targeting of proteins once considered “undruggable.” Unlike traditional small molecules that bind directly to a single protein, molecular glues act as mediators, stabilizing interactions between two proteins to drive a specific biological outcome. This breakthrough mechanism is particularly valuable for targeted protein degradation (TPD) and other therapeutic…
Precision Discovery and Structure-Guided Development of Molecular Glues
Molecular glues represent a groundbreaking approach in drug discovery, offering the unique ability to modulate or degrade traditionally “undruggable” targets by promoting or stabilizing protein-protein interactions. Unlike conventional small molecule inhibitors, molecular glues form ternary complexes involving two proteins and a small molecule, with their effectiveness largely driven by cooperativity—the synergistic enhancement of binding affinity through protein interaction.
Despite their therapeutic promise…