Knowledge Library
Biophysical and Structural Biology Methods Enable Fragment-based Covalent Ligand Discovery of Human BTK
Drug Discovery Chemistry Conference 2023 Powerful biophysical and structural biology tools enable the study of large numbers of covalent fragments and are opening up new possibilities in the treatment of various diseases. Here, Dr. Moran Jerabek-Willemsen, Head of Biophysics & Screening in WuXi Biology reports the results of a covalent FBDD project on Bruton’s Tyrosine …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 >
Computer-Aided Drug Discovery Services
Discovery and preclinical evaluations of GST-HG131, a novel HBV antigen inhibitor for the treatment of chronic hepatitis B infection
Chronic HBV infection (CHB) is a major contributor to liver-related deaths worldwide. The ultimate endpoint of CHB treatment is sustained HBV surface antigen (HBsAg) loss. Here, we report the design of a series of HBV surface antigen inhibitors which promotes reduction of HBV antigens in vitro and in vivo. https://pubmed.ncbi.nlm.nih.gov/36089112/
Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro
The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and thus is a target for drug discovery teams. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro with high in vivo efficacy in mice. One compound, WU-04, …Read More >
Optimization and Mechanistic Investigations of Novel Allosteric Activators of PKG1α
WuXi AppTec scientists recently contributed to a research article in the Journal of Medicinal Chemistry describing the optimization of a piperidine series of small molecules as novel allosteric activators of PKG1α (a compelling drug target for treatment of cardiovascular diseases). This study reveals a mechanism of action for these compounds consistent with cGMP-induced activation, including …Read More >
Large-scale synthesis of a Notum inhibitor employing a modified Sakai reaction as the key step
WuXi AppTec scientists recently contributed to a research article in the Royal Society of Chemistry describing the large-scale synthesis of a potent and selective inhibitor of Notum carboxylesterase (an enzyme that suppresses Wnt signaling pathways). By employing a modified Sakai reaction as the key step, a one-pot synthesis of this Notum inhibitor was developed, enabling …Read More >
WuXi Biology Fact Sheet
Expertise in all major disease areas and all major target classes, enabling discovery for all therapeutic modalities World class antiviral platform with an unequalled service capability and capacity in HBV and other viral diseases A global leader in DNA Encoded Library (DEL) screening, with innovative business models CAP-certified pathology and FACS capabilities supporting clinical biomarker …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 >
