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SpiroChem is at the forefront of this innovative approach. Our capabilities in the design and synthesis of proteolysis-targeting chimeras (PROTACs) and other protein degraders enable the selective targeting and degradation of disease-causing proteins. This innovative technology holds promise for the treatment of previously undruggable targets, offering new hope for patients and researchers alike.
Our team specializes in the design and synthesis of bifunctional molecules that recruit E3 ligases, such as CRBN and VHL, to target proteins, leading to their ubiquitination and degradation. We have extensive experience working with CRBN and VHL E3 ligases and their derivatives.
Our expertise extends to preparing libraries of PROTACs and CRBN-based GLUE degraders, providing a broad range of options for our clients. For PROTACs, we focus on optimizing the linker, which is not merely an inert chain of atoms linking two pharmacophoric parts but a crucial component often representing one-third of the molecular weight. The linker is essential for modulating the properties of the entire molecule, particularly its ability to cross membranes, which is essential to confer cellular activity. Properties we consider include length, lipophilicity, hydrophilicity, and conformational restrictions.
Our comprehensive support spans from initial concept and design of chemical tools to prove a concept, to final compound optimization, leveraging our expertise in computational chemistry to model the ternary structure and design optimal linkers. We also utilize our ability to generate exit vectors on complex molecules using our late-stage functionalization technologies, allowing us to rapidly identify the ideal anchor point for the linker on the ligand.
Whether applying a "sniper" approach, where available knowledge (such as a tool compound) serves as the basis for the rational design of the next generation of derivatives, or a combinatorial approach, where focused libraries of PROTACs with a chemically diverse range of linkers are prepared and tested to generate hits and readily available structure-activity relationship (SAR) data, SpiroChem is the ideal partner to embark on a PROTACs project.
With our extensive knowledge and state-of-the-art facilities, we help our clients overcome the challenges associated with this novel therapeutic approach, providing robust solutions that accelerate their research and development processes.
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