Peptides, and in particular macrocyclic peptides, are well known for their ability to disrupt protein-protein interactions (PPIs).  In this webinar, learn how DNA encoded library (DEL) screening can be used to discover peptide macrocycles that disrupt PPIs  Our speakers present a case study using the oncoprotein murine double minute 2 (MDM2). We will also highlight the …Read More >

RNA molecules are promising drug targets due to their genomic prevalence, disease involvement, and druggable complex structures. Successful examples include RNA-targeting small molecule drugs for spinal muscular atrophy (SMA), with on-going efforts in other RNA-related diseases. Here, Dr. Zhifeng Yu presents our toolbox for discovering RNA-targeting small molecules, with a focus on unique DNA-encoded libraries …Read More >

WuXi AppTec scientists recently contributed to a study which led to the discovery and optimization of a novel series of GST inhibitors. The authors used affinity mediated DEL selection against a privileged scaffold to identify a compound with potent inhibition against SjGST and GSTM2. SAR studies, coupled with X-ray crystallography and structural analysis, revealed that …Read More >

DELvision is a powerful DNA encoded library (DEL)-based toolset for AIphaFold-assisted drug discovery and target sciences. In contrast to conventional screens where the target space is low-dimensional, DELvision comprises a high-dimensional map of binding relationships between small molecules and protein targets. As such, this rich data universe enables simultaneous characterization of targets and exploration of …Read More >

As reported in Business Wire: DNA-Encoded Libraries (DELs) and NanoBRET Target Engagement Assays Accelerate Drug Discovery: “The authors demonstrate that DELs can benefit chemical biologists who require verification of live cell target engagement for their protein of interest. This is particularly beneficial for understudied protein classes that may not have existing chemical probes. Additionally, they …Read More >

WuXi AppTec scientists recently contributed to a research article in Cell Chemical Biology demonstrating the successful conversion of ligands identified from DNA-encoded library (DEL) screening into highly functional, cell-active, bioluminescence resonance energy transfer (BRET) probes. The authors show that analyzing preliminary DEL hits based on target occupancy data generated in live, intact cells is an …Read More >

Macrocyclic peptides are an emerging molecular class for targeting intracellular protein–protein interactions (PPIs) and for providing an oral modality for drug targets. Herein, we use DNA-encoded cyclic peptide libraries to discover a neutral nonapeptide, UNP-6457, that inhibits MDM2–p53 interaction with an IC50 of 8.9 nM. These studies showcase how tailored DEL libraries can directly yield …Read More >

Drug Discovery Chemistry Conference 2023 WuXi AppTec has developed technologies to facilitate RNA small molecule screening, an exciting frontier in drug discovery. SHAPE-MaP is applied to determine RNA structure and dynamics and verify small molecule binding. We utilize the “DNA-Zipper” strategy to enable DNA-encoded libraries to identify RNA binders. With other technologies including fragment-based drug …Read More >

Drug Discovery Chemistry Conference 2023 DNA-Encoded library (DEL) screening is now commonly used in the pharmaceutical industry to find novel chemical matter that modulates protein targets of interest.  Point-by-point, Dr. Alex Satz, Executive Director, WuXi Biology will discuss the primary challenges and limitations of DEL screening, and concisely state the current abilities of the technology …Read More >