The identification of small molecule protein ligands remains a key hurdle for the validation and translation of novel targets pivotal to the successful development of new medicines. However, the costly resources to deliver an effective compound screening campaign and the contractual commitment to the screening organisations, limit the development of drug discovery projects for biomedical researchers.
To address this capability gap we are establishing a small-molecule discovery workflow based on the DNA-encoded library (DEL) chemistry technology that will provide cost-free and commitment-free access to high-throughput screening for academic research groups.
The technology allows preparation of millions of druglike molecules each linked to a unique DNA sequence, which are selected as a mixture for binding affinity against a protein. Since each DNA tag encodes the structure of its associated molecule, high-affinity protein binders can be identified by DNA sequencing, making DEL screening a simpler and affordable hit discovery strategy.
We have developed the chemistry to enable synthesis of spatially and chemically diverse libraries, and so far, we have completed the synthesis of three libraries summing up to 6 million compounds.
The discovery workflow has been validated by selections against carbonic anhydrase CA IX, IRE1.
