DEL technology enables the simultaneous screening of millions or billions of compounds in a single tube by covalently linking each small molecule with a unique DNA sequence. Traditional DEL screening primarily focuses on identifying non-covalent binding molecules, where interactions with the target are reversible. In contrast, DNA‑encoded covalent library is an ultra‑high‑throughput screening library developed on the basis of conventional DNA‑encoded library technology. It incorporates controllable electrophilic covalent warheads capable of forming irreversible covalent bonds with amino acid residues at the active sites of target proteins, including Cys, Lys, Ser, Tyr, and others. This covalent binding enhances binding affinity, prolongs residence time at the target site, and has the potential to overcome challenges associated with traditional non-covalent inhibitors, such as drug resistance or off-target effects.

Each compound in the library contains both a binding domain and an electrophilic warhead. It first recognizes and binds to the target through non covalent interactions, and then forms a stable covalent bond with key amino acid residues to achieve irreversible inhibition. This library is specifically designed for the discovery of potent, long lasting, and highly selective covalent inhibitors, particularly for undruggable targets such as kinases, GPCRs, proteases, and mutant oncoproteins. Each molecule is uniquely labeled with a DNA barcode for molecular identification and sequencing decoding.

This library is an advanced and highly diverse collection, consists of 35 independent sub-libraries with a total scaleof 14 million compounds, It incorporates over 14 experimentally validated covalent warheads capable of targeting cysteine, lysine, arginine, aspartic acid and glutamic acid. This library is constructed with diverse drug like core scaffolds and integrated controllable covalent warheads, it features structural diversity, reaction spec