Knowledge Library
Negative allosteric modulation of the µ-opioid receptor
DNA-encoded libraries from WuXi AppTec were used in a “steered” screening against either inactive or active μ-opioid receptors in parallel, to find novel negative allosteric modulators of this receptor. The molecule discovered via DEL screening not only shows direct and effective in vitro and in vivo potency, but also helps elucidate the mechanism of negative allosteric modulation of GPCRs. This discovery …Read More >
Dianthus Platform: Screening for CRBN-DDB1 Proteolysis-Targeting Chimeras and Molecular Glues
Cereblon (CRBN) forms an E3 ligase complex together with DDB1, CUL4, and RBX1. CRBN functions as a substrate receptor of this complex for the recognition and binding of proteins targeted for ubiquitination and proteasomal degradation. To support the discovery of CRBN-DDB1 proteolysis-targeting chimeras and molecular glues, WuXi AppTec offers an integrated platform of ready-to-go assays …Read More >
Discovery of CVN636: A Highly Potent, Selective, and CNS Penetrant mGluR7 Allosteric Agonist
The metabotropic glutamate receptor mGluR7 is widely expressed throughout the CNS and has been implicated in numerous CNS disorders. WuXi AppTec scientists recently contributed to a study which led to the identification, optimization, and characterization of a highly potent, novel mGluR7 allosteric agonist, designated CVN636. The authors show that CVN636 has high selectivity toward mGluR7, …Read More >
Translational Pharmacology of CNS and Metabolic Disorders for Testing New Modality Therapies
Animal studies may provide a close approximation to humans when addressing the key challenge of clinical translatability. In the preclinical setting, new insights into disease models and mechanisms are crucial to efficacy studies. In this webinar, Dr. Deming Xu, Chief Pharmacologist, Executive Director, and Head of In Vivo Pharmacology of WuXi AppTec Discovery Biology will …Read More >
Discovery of Potent and Selective Dual Leucine Zipper Kinase/Leucine Zipper-Bearing Kinase Inhibitors
Dual leucine zipper kinase (DLK) and leucine zipper-bearing kinase (LZK) have emerged as key regulators of neuronal degeneration and axon growth. WuXi AppTec scientists recently contributed to a research article in the Journal of Medicinal Chemistry demonstrating the use of ligand- and structure-based drug design approaches to discover an amino-pyrazine chemical series of DLK and …Read More >
Ligand Finding and Chemistry Workflows for Targeted Protein Degradation
This webinar will focus on aspects related to PROTAC discovery and chemistry workflows, such as ligand finding strategies, synthesis optimization, and linker design. Successful development of bifunctional molecules requires a deep understanding of multiple processes, including biophysical events which dictate induced proximity and how technologies such as DNA-encoded libraries (DEL) can be leveraged to identify …Read More >
Biological Characterization and Development Workflows for Targeted Protein Degradation
This webinar will focus on PROTAC biology workflows, such as in vitro screening assays, in vivo testing, and optimization of DMPK properties. Topics will include the best use of biochemical assays to measure binary/ternary complex formation, cell-based assays to assess target engagement and degradation, strategies for enhancing drug delivery and formulation, and PK/PD evaluation of …Read More >
Discovery Newsletter Special New Year Edition 2023
WuXi AppTec in vitro Neuroscience Services
Neurological disorders, such as neurodegenerative diseases, epilepsy, chronic pain, psychiatric disorders, are one of today’s largest unmet medical needs. However, due to poor disease and target understanding, Neuroscience drug discovery can be very challenging. An open access research platform with dedicated neuroscience specialists and integrated services will be an ideal partner throughout your drug discovery …Read More >