Knowledge Library
Small Molecule Reactivator of p53 Y220C Mutant
Mutant p53 is one of the most attractive targets for new anti-cancer drugs. Although traditionally regarded as difficult to drug, several new strategies have recently become available for targeting the mutant protein. One of the most promising of these involves the use of low molecular weight compounds that promote refolding and reactivation of mutant p53 …Read More >
Strategies for Screening and Characterizing Targeted Covalent Inhibitors
With advancements in drug design, there is resurging interest in drugs that form covalent bonds with their targets, often referred to as targeted covalent inhibitors (TCIs). In this webinar, experts discuss innovative approaches to screen for covalent binders, strategies for the synthesis of covalent warheads, and assays to optimize the ADME/DMPK properties of these molecules. …Read More >
Preclinical Evaluation of the SARS-CoV-2 Mpro Inhibitor RAY1216
WuXi AppTec scientists contributed to a research article in the journal Nature Microbiology, which characterized a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro). In a human ACE2 transgenic mouse model, this inhibitor (designated RAY1216) exhibited antiviral activities against SARS-CoV-2 comparable to those of nirmatrelvir, but with improved pharmacokinetics.
PROTAC Optimization Strategies
What if a constructed PROTAC with a confirmed high-affinity warhead doesn’t work as expected? That means we need to take a closer, more careful look at how it’s designed and how it works. In this video, our expert from WuXi Biology shares strategies to address such an R&D scenario.
Addition of Covalent Warhead and DEL-Generated Hit Fragmentation Empower FBDD
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 >
One Stop Target-to-Hit Platform: CDKs and CDK-Cyclin Complexes
Cyclin-dependent kinases (CDKs) and their cyclin regulatory subunits form complexes that are essential for driving abnormal growth processes in cancer cells, making these molecules important targets for cancer treatment. To support the discovery of novel CDK inhibitors, WuXi AppTec offers a comprehensive platform of biophysical and biochemical assays to accelerate hit finding and lead optimization …Read More >
Biophysical and Structural Biology Methods Enable Fragment-Based Ligand Discovery
Powerful biophysical and structural biology tools enable the study of large numbers of fragments and are opening new possibilities in the treatment of various diseases. In this webinar, WuXi AppTec presents the results of a conventional and covalent fragment-based drug discovery screen, and our expert speaker discusses how orthogonal biophysical and structural methods enable the …Read More >
Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor
DNA-dependent protein kinase (DNA-PK) plays an important role in the overall survival and proliferation of cells, making this enzyme an intriguing target for the treatment of a variety of cancers. In our latest publication, WuXi AppTec scientists contributed to the discovery and characterization of ZL-2201, a potent and highly selective small molecule DNA-PK inhibitor. In …Read More >
Osimertinib-Resistant Cell Lines and Models
Despite the robust clinical activity exerted by osimertinib, a majority of patients eventually exhibit disease progression while receiving this drug. Resistance to osimertinib includes both on-target and off-target mechanisms. With the use of osimertinib for advanced EGFR-mutant NSCLC increasing, the development of targeted therapies toward osimertinib resistance represents an unmet medical need. To support research …Read More >