Knowledge Library
Baricitinib treatment reduces the expansion of CD8+ T cells in C3H mice with skin grafts-induced alopecia areata
SITC Poster #452: Alopecia areata (AA) is an autoimmune disease characterized by patchy and sudden hair loss without scarring, resulting in a heavy psychological burden on patients. To better understand the pathogenesis and treatment of alopecia areata, we developed a skin grafts-induced alopecia areata model to provide a reproducible, reliable animal model for AA research. …Read More >
Administration of JAK and TYK2 inhibitors successfully ameliorate the severity of T cell transfer-induced colitis in mice
SITC Poster #446: Inflammatory bowel disease (IBD) is recognized as an autoimmune disorder characterized by chronic inflammation of the digestive tract. The pathogenesis of IBD is not fully understood and can repeatedly relapse despite clinical therapy. The T cell transfer-induced colitis model enables the study of early inflammation and immunological responses in the colon, such …Read More >
Upregulation of drug metabolism enzymes mediates ADC resistance in a HER2-positive cancer cell line
SITC Poster #1162: Enhertu is currently approved for the treatment of patients with HER2-positive breast cancer, gastric cancer, or HER2-mutant non-small cell lung cancer. However, despite Enhertu’s clinical benefits, most patients inevitably experience disease progression and mortality. Understanding drug resistance mechanisms can aid in developing new treatment strategies for drug-resistant clinical patients. In this study, …Read More >
Covalent Fragment-based Drug Discovery: BTK Inhibitors
At the Covalent Drug Discovery 2023 Summit and Fragments 2024 Conference, we presented a case study on Bruton’s tyrosine kinase (BTK) and demonstrated how biochemical, biophysical, and structural biology methods were used to confirm hits, characterize binding kinetics, and evaluate the mode of interaction of covalent BTK inhibitors. Our hit-to-lead workflow showcases the importance of bioanalytical …Read More >
Colitis-Associated Cancer Mouse Model
The cumulative impact of chronic inflammation in patients with inflammatory bowel disease (IBD) predisposes them to the development of IBD-associated colorectal cancer. To support drug discovery research in this area, WuXi AppTec has developed a colitis-associated cancer mouse model to reflect the human colon’s carcinogenesis pattern derived from inflammation. Key features of this model include …Read More >
Parallel Purification of High-Quality Therapeutic Targets
Learn about our semi-automated chromatography platform for parallel purification of high-quality therapeutic targets. At PEGS Europe 2023, WuXi AppTec scientists described an automated workflow integrated with a serial size exclusion platform, resulting in a complete purification scheme for the rapid purification of high-quality proteins expressed in E. coli, insect cells, and mammalian cells. This approach …Read More >
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 >
Combined Inhibition of KRAS G12C and PD1 Boosts Therapeutic Efficacy via Conditioning of Tumor Microenvironment
SITC Poster #466: Mutant KRAS is linked to PD-L1 expression, and oncogenic RAS signaling promotes an immunosuppressive tumor microenvironment by upregulating PD-L1 expression. Consequently, combining KRAS G12C inhibitors with immune checkpoint blockers shows promising benefits. To better understand the mechanisms underlying the combined inhibition of KRAS G12C inhibitor AMG 510, and anti-PD-1 antibody nivolumab, LU-01-0361 …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 >