Knowledge Library
Rare Disease Therapeutics: Accelerating Development and Improving Access
Advances in the understanding of rare disease biology, coupled with innovative technology and therapeutic platforms, has led to progress in the research and development of drugs for rare diseases. Despite these advances, many rare diseases still lack useful treatments and the need for new approaches remains high. In this webinar, we will discuss important trends …Read More >
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 >
Establishment of EGFR TKI-Resistant Tumor Models
Despite improvement in clinical outcomes observed with the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), long-term prognosis remains unfavorable due to the development of either intrinsic or acquired resistance. Understanding the mechanisms underlying this resistance is vital for designing strategies to address this challenge, and one approach involves the establishment of …Read More >
iMN041: Prodrug with a Unique Antitumor Immune Response
WuXi AppTec scientists contributed to a research article in the journal Translational Medicine Communications which characterized the antitumor immune responses generated by iMN041, a prodrug of a DNA methyl transferase/ribonucleotide reductase inhibitor. This study also assessed the efficacy of iMN041 in mouse xenografts of human clear cell renal cell cancer, pancreatic cancer, and triple negative …Read More >
DNA-Compatible Cyclizations
The recent publication in the journal Organic Letters, ‘DNA-Compatible Cyclization Reaction to Access 1,3,4-Oxadiazoles & 1,2,4-Triazoles‘ by our WuXi Biology DEL team, introduces two novel DNA-compatible reactions, successfully incorporating bioactive cores 1,3,4-oxadiazoles and 1,2,4-triazoles into the DEL library. These cores are reported to show broad ranges of biological activities, such as antiviral, anti-inflammatory, anticancer, antifungal, …Read More >
EML4-ALK Cell Lines and In Vivo Models
The EML4-ALK fusion gene occurs in approximately 5% of non-small-cell lung cancers (NSCLCs), making this oncogene an important drug target. The development of ALK tyrosine kinase inhibitors (ALK-TKIs) has been a major advance in treating NSCLC with this fusion gene, but acquired resistance to ALK-TKIs ultimately limits their use. To support the development of next-generation …Read More >
High-Dimensional Flow Cytometry Platform
High-dimensional (HD) flow cytometry allows researchers to perform deep phenotyping of immune cells at the single cell level with increased accuracy and sensitivity. This technology enables complex pathway characterization and data integration for the identification of biomarkers used in immunotherapy. WuXi AppTec offers a comprehensive panel of HD flow cytometry services, with more than 100 …Read More >
STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
The contribution of the X-ray crystallography team from our WuXi AppTec site in Germany was acknowledged in a recent study published in the journal Cancer Discovery. In this study, the authors show that compound STX-478, an allosteric PI3Kα inhibitor, selectively targets prevalent PI3Kα helical- and kinase-domain mutant tumors. STX-478 demonstrated robust efficacy in human tumor …Read More >
How to Accelerate the Synthesis of PROTACs: Strategies and Case Studies
Introduction: Targeted Protein Degradation (TPD) has emerged as a promising therapeutic modality due to its potential to develop therapeutics for previously undruggable targets and address the resistance issues of small molecule inhibitors. Central to this strategy is the novel protein-degradation approach represented by proteolysis-targeting-chimeras (PROTACs), which induce targeted protein degradation through the ubiquitin-proteasome system (UPS). …Read More >