G-protein coupled receptors (GPCRs) play a pivotal role in signaling pathways, and these transmembrane proteins represent an important drug target class. The majority of approved drugs that target GPCRs bind to traditional orthosteric sites. In a recent publication in Nature, Professor Brian Kobilka and his team at Stanford University successfully identified selective negative allosteric modulators …Read More >

In the last decade, targeted protein degradation (TPD) technology has become one of the most promising methods to remove specific disease-related proteins using cellular self-destruction mechanisms. WuXi AppTec has built a robust TPD discovery platform, allowing for in-depth biological and biophysical characterization of monovalent (molecular glue) and bivalent (PROTAC®) molecules through the use of target …Read More >

WuXi AppTec offers a comprehensive platform of in silico drug discovery services to accelerate the process of hit finding and hit-to-lead optimization.  We provide access to virtual chemical spaces built from our library of novel drug-like scaffolds, to support virtual screening and structure-based virtual screening (SBVS). Advances in ML-empowered virtual screening allows project teams to …Read More >

In addition to identifying chemical starting points for early drug discovery processes, DNA-encoded library (DEL) technology has now expanded to new applications, including the discovery of bifunctional affinity ligands historically considered difficult to develop. At the 2024 Gordon Research Conference, WuXi AppTec presented a poster describing how DEL can enable the rapid discovery of novel …Read More >

Despite the availability of modern screening technologies, identification and optimization of hits against poorly druggable targets remains a significant challenge for drug discovery teams.  Generating hit matter and reference compounds with one screening technology and then screening with a second technology has the potential to be a powerful tool for researchers. At this year’s Oxford …Read More >

WuXi AppTec scientists published a study in the open access archive ChemRxiv describing the discovery of highly selective, novel, heme oxygenase-1 (HO-1) targeting molecules. HO-1, primarily a heme-degrading enzyme, has been identified as a potential therapeutic target in diseases such as cancer and neurodegenerative disorders. Here, we report the discovery of five series of novel …Read More >

Fragment-based drug discovery (FBDD) is one of the most well-developed approaches for projects starting from small, low-affinity compounds.  At the SLAS 2024 meeting in Boston, WuXi AppTec presented a poster reporting on the assembly of a covalent fragment library that is suited to tackle protein targets via serine, lysine, and cysteine residues. In a case …Read More >

Due to the special configuration of the DNA encoded library (DEL), each DEL molecule carries a DNA sequence encoding its identity through a bifunctional linker. The linkers that are considered “redundant” and “troublesome” in traditional drug discovery actually offer innate advantages in many application scenarios. In this article, we review how to utilize DNA-encoded libraries …Read More >

At the Covalent Drug Discovery 2023 Summit and Fragments 2024 Conference, we presented a case study on Bruton’s tyrosine kinase (BTK) and demonstrated how biochemical, biophysical, and structural biology methods were used to confirm hits, characterize binding kinetics, and evaluate the mode of interaction of covalent BTK inhibitors. Our hit-to-lead workflow showcases the importance of bioanalytical …Read More >