Knowledge Library

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 >

Resource Type: Latest Science Poster
Resource Topic: Cells and Protein Science

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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 >

Resource Type: Latest Science Publication
Resource Topic: Central Nervous System & Pain DNA-Encoded Library (DEL) Hit Finding Small Molecules

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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 >

Resource Type: Latest Science Poster
Resource Topic: Antibodies Oncology Small Molecules Tumor Models

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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 >

Resource Type: Latest Science Publication
Resource Topic: Cell-based Assays Hit-to-Lead Lead Optimization Oncology Tumor Models

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Osimertinib-Resistant Cell Lines and Models

Despite the robust clinical activity exerted by osimertinib, a majority of patients eventually exhibit disease progression while receiving this drug.  Resistance to osimertinib includes both on-target and off-target mechanisms.  With the use of osimertinib for advanced EGFR-mutant NSCLC increasing, the development of targeted therapies toward osimertinib resistance represents an unmet medical need.  To support research …Read More >

Resource Type: Latest Science Presentation
Resource Topic: Lead Optimization Oncology Tumor Models

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Control of the Antitumor Activity and Specificity of CAR T Cells via Organic Adapters Covalently Tethering the CAR to Tumor Cells

On-target, off-tumor toxicity is a specific type of toxic side effect that limits the anticancer applicability of chimeric antigen receptor (CAR) T cells. In our latest publication, WuXi AppTec scientists contributed to a study describing how the tumor-targeting specificity and activity of T cells with a CAR (consisting of an antibody that catalytically forms a …Read More >

Resource Type: Latest Science Publication
Resource Topic: CAR-T Cell Oncology

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Structure-Based Design and Synthesis of Potent and Selective KRAS G12D Inhibitors

The KRAS G12D mutation subtype is present in over 40% of pancreatic ductal adenocarcinomas (PDAC), making this an important drug target.  WuXi AppTec scientists recently contributed to a research article in ACS Med. Chem. Letters describing the optimization of a series of potent and selective KRAS G12D inhibitors through a structure-based drug design approach.  The …Read More >

Resource Type: Latest Science Publication
Resource Topic: Hit-to-Lead Lead Optimization Oncology Small Molecules Structural Biology

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Anti-Tumor Nucleic Acid Drug Discovery Platform

Successful application of nucleic acid therapeutics faces many challenges, including delivery efficiency and off-target effects.  To address these challenges, WuXi AppTec offers a full suite of nucleic acid-related services, including target validation, in vitro screening and cell-based functional assays, drug exposure analysis, biodistribution evaluation, PK/PD/efficacy testing, and safety assessment.  Leverage our comprehensive platform to accelerate …Read More >

Resource Type: Latest Science Presentation
Resource Topic: Cell-based Assays in vivo Pharmacology in vivo Toxicology Oligonucleotides Oncology

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Enhertu-Induced Resistant Tumor Models

Antibody‒drug conjugates (ADCs), which combine the advantages of monoclonal antibodies with precise targeting and payloads, show great potential as cancer therapies.  However, primary and secondary resistance is frequently observed, and development of next generation ADCs necessitates the establishment of resistant tumor models.  WuXi AppTec offers validated, Enhertu-induced resistant tumor models to support project teams focused …Read More >

Resource Type: Latest Science Presentation
Resource Topic: Antibody Drug Conjugate Oncology Tumor Models

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