Knowledge Library
USP7 Inhibitors Reveal a Differentiated Mechanism of p53-Driven Anti-Cancer Activity
Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that cleaves ubiquitin from a range of substrates, shielding them from degradation by the proteasome. USP7 activity has been implicated in cancer progression and its overexpression is associated with tumor aggressiveness and poor prognosis in a variety of cancer types, making USP7 inhibition an attractive strategy for …Read More >
A µ-Opioid Receptor Modulator that Works Cooperatively with Naloxone
G-protein coupled receptors (GPCRs) play a pivotal role in signaling pathways, and these transmembrane proteins represent an important drug target class. The majority of approved drugs that target GPCRs bind to traditional orthosteric sites. In a recent publication in Nature, Professor Brian Kobilka and his team at Stanford University successfully identified selective negative allosteric modulators …Read More >
CRBN Structural Biology Services
Targeted protein degradation of disease-causing proteins by the E3 ligase cereblon (CRBN) represents a new therapeutic strategy for addressing challenging-to-treat diseases. To support drug discovery programs, we have established off-the-shelf crystallization and cryo-EM systems to enable the determination of high-resolution X-ray crystal structures with a short turnaround time. Together with our protein production service and …Read More >
mRNA-Encoded Modulators Suppress Tumor Growth
Unlike conventional protein-targeted therapies, nucleic acid therapeutics have the potential for long-lasting effects and greater target specificity. WuXi AppTec provides a comprehensive platform to support the discovery of mRNA drugs. Our services include mRNA design and production, assessment of mRNA delivery systems, in vitro evaluation, and determination of in vivo efficacy and biodistribution. At AACR …Read More >
Recent Advances in HTE and Flow Chemistry
High throughput experimentation (HTE) is frequently employed to identify reaction conditions for challenging transformations, giving access to a diverse array of medicinal chemistry targets. In parallel to using conventional batch reactions, we also incorporate flow chemistry into early phase synthesis to help with reaction selectivity and optimization, up-scaling, and solving specific chemical problems. In this …Read More >
Discovery Platform for Targeted Protein Degradation
In the last decade, targeted protein degradation (TPD) technology has become one of the most promising methods to remove specific disease-related proteins using cellular self-destruction mechanisms. WuXi AppTec has built a robust TPD discovery platform, allowing for in-depth biological and biophysical characterization of monovalent (molecular glue) and bivalent (PROTAC®) molecules through the use of target …Read More >
OncoWuXi Express: Efficacy of DLL3 CAR-T in SHP-77 Tumor Models
OncoWuXi Express: Evaluation of DLL3 CAR-T in SHP-77-Luc Tumor Models Introduction: OncoWuXi Express will continue to keep you informed about updates to our online tumor model database (OncoWuXi Database), as well as our recent progress in cancer and autoimmune research. In this issue, we showcase our DLL3 CAR-T cell preparation and evaluation of their anti-tumor …Read More >
Creating a Biological Switch Using DEL Technology
In addition to identifying chemical starting points for early drug discovery processes, DNA-encoded library (DEL) technology has now expanded to new applications, including the discovery of bifunctional affinity ligands historically considered difficult to develop. At the 2024 Gordon Research Conference, WuXi AppTec presented a poster describing how DEL can enable the rapid discovery of novel …Read More >
Recent Insights into Immuno-Oncology
The efficacy of CAR-T therapy is substantially influenced by the tumor microenvironment. This is particularly evident when PD-L1 is activated through CAR-T, leading to the inhibition of CAR-T cell activity via the PD-1 pathway. At the 2024 Recent Insights into Immuno-Oncology Conference, WuXi AppTec presented a poster describing an engineered CAR-T therapy that targets mesothelin …Read More >