Knowledge Library
Rational Design and Optimization of a Potent IDO1 PROTAC
Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that metabolizes tryptophan, and its activity can lead to immunosuppression, thereby allowing tumors to evade the immune system. IDO1 can also suppress the immune response through mechanisms independent of its enzyme activity, and this may be difficult to target with current inhibitors. Drugs targeting only IDO1 enzyme activity …Read More >
Development, Characterization, and Therapeutic Utility of Paclitaxel-Resistant Models
Despite the excellent clinical response to paclitaxel therapy, drug resistance inevitably develops in subsequent treatments. The development of targeted therapies for overcoming paclitaxel resistance represents an unmet medical need. Although not fully understood, the mechanisms for resistance to paclitaxel include drug efflux transporter overexpression, altered apoptotic gene expression, and changes associated with microtubules to reduce …Read More >
Women’s Health Platform
Women’s health care is crucial not only for the well-being of individual women but also for the health and prosperity of families and communities. Despite significant medical advancements, there remains a concerning gap in the availability of effective drugs for common women-related diseases such as endometriosis, menopause syndromes, polycystic ovary syndrome (PCOS), and various forms …Read More >
Targeting FAK Improves the Tumor Uptake of ADCs
Antibody-drug conjugates (ADCs), exemplified by HER2-targeted Enhertu and TROP2-targeted Trodelvy, have demonstrated significant therapeutic potential in cancers. However, a subset of patients remains refractory to ADC treatment. WuXi AppTec contributed to a research article which demonstrated that excessive cancer-associated fibroblasts (CAFs) can form a fibrotic barrier within a tumor microenvironment, impeding the tissue uptake of …Read More >
BRCA2 Deficient DLD-1 Model
BRCA1 and BRCA2 proteins are key components of the homologous recombination repair pathway for repairing double-stranded DNA breaks. Mutations in BRCA genes can significantly increase the risk of certain cancers such as breast, ovarian, pancreatic, and prostate cancer. To mimic the effects of BRCA2 deficiency in humans, WuXi Biology has constructed a BRCA2 deficient mouse …Read More >
OncoWuXi Express: Evaluation of T Cell Engagers
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 would like to share with you our preclinical pharmacological evaluation platform for T cell engagers. https://onco.wuxiapptec.com Introduction T-cell engagers (TCEs) are …Read More >
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 >
BaF3 Models Carrying HER2 Mutations
Frequently observed in NSCLC patients, the 4 amino acid YVMA insertion is the most common type of HER2 exon 20 insertion mutation. A secondary mutation, C805S, often develops as a mechanism of resistance to HER2 tyrosine kinase inhibitors (TKIs) such as poziotinib, where the C805 residue is crucial for drug binding. The presence of a …Read More >
PRMT5 Related Tumor Models
Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. MTAP deletions occur in approximately 10 – 15% of all human cancers. When the MTAP gene is deleted, methylthioadenosine (MTA) accumulates and selectively inhibits PRMT5. This creates a synthetic lethal dependence on PRMT5 in MTAP-deleted tumors. As a potential …Read More >