Chemical inducers of proximity (CIPs) are small molecules that induce the proximity of two biological targets, usually proteins. Molecular glues and PROteolysis TArgeting Chimeras (PROTACs®) are among the best-known CIPs. These molecules utilize the endogenous E3-based proteolysis pathway to induce proximity between the target protein and E3 ligase, thereby triggering targeted protein degradation. At the …Read More >

Introduction Membrane proteins are essential for various cellular processes, including energy conversion, signal transduction, and disease progression. Efficient and accurate identification and screening of these proteins are vital for the development of small-molecule therapeutics targeting membrane proteins. In recent years, Affinity Selection Mass Spectrometry (ASMS) has become a powerful tool for studying membrane protein-small molecule …Read More >

Introduction: New modalities, such as molecular glues, require robust screening strategies to identify and develop the most promising candidates efficiently. In this article, we spotlight Affinity Selection Mass Spectrometry (ASMS), a versatile and cost-effective high-throughput screening technique used in drug discovery. ASMS: A Powerful High-throughput Screening Technology Since the mid-1990s, ASMS has emerged as a …Read More >

The safe production of cultivated plants is threatened by various fungal diseases. NIS1 is a secreted effector protein produced by various fungal pathogens. BAK1 is a plant receptor-like kinase that plays a crucial role in recognizing pathogen-associated molecules like NIS1. Understanding the interaction between NIS1 and BAK1 is important for studying plant defense mechanisms against …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 >

GLUT1 serves as the conduit for transporting glucose from the extracellular milieu into the cell, thereby fueling cellular physiological activities via glucose metabolism. Its overexpression has been documented in various tumor cells, establishing GLUT1 as a promising therapeutic target. During an ASMS screening of GLUT1, a counter screen was introduced to effectively mitigate false positives …Read More >

Molecular glues possess the remarkable ability to induce protein-protein interactions. In the pursuit of targeting the CDK12/CCNK/DDB1 complex, an ASMS screening strategy was employed, resulting in the successful identification of two active molecular glues from a subset of 2000 small molecules within the WuXi AppTec compound library. Validation efforts revealed compelling findings: the two small …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 >