Welcome to your September Newsletter!
WuXi Discovery Services
Driving drug discovery through world-class capabilities, dedicated collaborative teams, and scientific excellence.
Combating Drug Resistance in Cancer Therapy
Over time, tumors develop drug resistance, resulting in treatment failure. This resistance is inherent to the tumor cells themselves, as well as tied to factors within the tumor microenvironment. To bolster the research of cancer drugs and to emulate real-world clinical scenarios of tumor resistance, WuXi Biology has developed a platform of preclinical drug resistance models leveraging in vivo and in vitro methodologies.
Discovery of SARS-CoV-2 Papain-like Protease Inhibitors
The SARS-CoV-2 papain-like protease (PLpro) is responsible for polyprotein processing, which is required for the generation of a functional viral replicase. WuXi AppTec scientists recently contributed to a study on the discovery of potent, selective, and orally bioavailable SARS-CoV-2 PLpro inhibitors with robust efficacy in a mouse-adapted model of COVID-19 infection.
Novel DEL Hit That Binds in the Cbl-b SH2 Domain
Casitas B lymphoma-b (Cbl-b), has been identified as an attractive target for cancer immunotherapy due to its role in promoting an immunosuppressive tumor environment. WuXi AppTec contributed to a study which identified a hit compound following screening of a DNA-encoded library (DEL) using activated Cbl-b. The authors employed a structure-based approach to optimize this hit, resulting in a compound with measurable cell activity.
Pulmonary Disease Platform
WuXi AppTec offers a comprehensive platform of pulmonary disease-related services. We provide a wide panel of validated disease models, including pulmonary fibrosis, pulmonary arterial hypertension, asthma, and chronic obstructive pulmonary disease. Our experts utilize advanced technologies with fully equipped invasive and non-invasive systems, such as the pulmonary function test system.
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Oncogenic Virus-associated Tumor Models
Approximately 10% of cancers globally are attributed to viral infections, primarily from viruses like HPV, EBV, HBV, and HCV. As viral cancers have viral-specific targets, there is potential to use these targets as specific antigens for cancer immune therapy. WuXi AppTec offers a panel of oncovirus-related tumor models and services. Our platform includes syngeneic, CDX, and PDX models, representing multiple cancer types such as lymphoma, cervical, and liver cancer.
Ready-to-Go PDX Panels
Patient-derived xenograft (PDX) models preserve the original tumor's molecular, histopathological, and pharmacological characteristics, reflecting the heterogeneity and diversity of human tumors. WuXi Biology has developed over 1,500 PDX models across 30 cancer types. These models are comprehensively characterized to meet the high standards of translational cancer research. At WuXi Biology, several ready-to-go PDX panels with specific designs based on cancer type or target information are routinely maintained in live mice for a more cost-effective operation and quicker turn-around time of PDX panel studies.
One Stop Target-to-Hit Platform: RAS Family
The RAS family of small GTPases are among the most frequently mutated oncogenes in human cancer. Previously viewed as undruggable, the recent FDA approval of two KRAS G12C-selective inhibitors has offered real promise to the development of anti-RAS therapies, including mutation-specific strategies.
To support the discovery of novel KRAS inhibitors, WuXi AppTec offers a comprehensive panel of ready-to-go biophysical assays, nucleotide exchange assays, and established X-ray crystallography protocols. Our RAS protein production platform encompasses a broad range of KRAS variants, including G12C, G12D, G12V, and “Cys-light” variants to study covalent inhibitors.