Knowledge Library

Integrated Screening in Hit Identification

Despite the availability of modern screening technologies, identification and optimization of hits against poorly druggable targets remains a significant challenge for drug discovery teams.  Generating hit matter and reference compounds with one screening technology and then screening with a second technology has the potential to be a powerful tool for researchers. At this year’s Oxford …Read More >

Resource Type: Latest Science, Poster
Resource Topic: DNA-Encoded Library (DEL), Hit Finding, Hit-to-Lead, Small Molecules

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Addition of Covalent Warhead and DEL-Generated Hit Fragmentation Empower FBDD

Fragment-based drug discovery (FBDD) is one of the most well-developed approaches for projects starting from small, low-affinity compounds.  At the SLAS 2024 meeting in Boston, WuXi AppTec presented a poster reporting on the assembly of a covalent fragment library that is suited to tackle protein targets via serine, lysine, and cysteine residues. In a case …Read More >

Resource Type: Latest Science, Poster
Resource Topic: DNA-Encoded Library (DEL), Fragment-Based Drug Discovery, Hit Finding, Hit-to-Lead, Lead Optimization, Small Molecules

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DNA-Compatible Cyclizations

The recent publication in the journal Organic Letters, ‘DNA-Compatible Cyclization Reaction to Access 1,3,4-Oxadiazoles & 1,2,4-Triazoles‘ by our WuXi Biology DEL team, introduces two novel DNA-compatible reactions, successfully incorporating bioactive cores 1,3,4-oxadiazoles and 1,2,4-triazoles into the DEL library. These cores are reported to show broad ranges of biological activities, such as antiviral, anti-inflammatory, anticancer, antifungal, …Read More >

Resource Type: Latest Science, Publication
Resource Topic: Discovery Chemistry, DNA-Encoded Library (DEL), Small Molecules

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STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts

The contribution of the X-ray crystallography team from our WuXi AppTec site in Germany was acknowledged in a recent study published in the journal Cancer Discovery. In this study, the authors show that compound STX-478, an allosteric PI3Kα inhibitor, selectively targets prevalent PI3Kα helical- and kinase-domain mutant tumors. STX-478 demonstrated robust efficacy in human tumor …Read More >

Resource Type: Latest Science, Publication
Resource Topic: Oncology, Small Molecules, Structural Biology, Structural Biology, X-ray Crystallography

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How to Accelerate the Synthesis of PROTACs: Strategies and Case Studies

Introduction: Targeted Protein Degradation (TPD) has emerged as a promising therapeutic modality due to its potential to develop therapeutics for previously undruggable targets and address the resistance issues of small molecule inhibitors. Central to this strategy is the novel protein-degradation approach represented by proteolysis-targeting-chimeras (PROTACs), which induce targeted protein degradation through the ubiquitin-proteasome system (UPS). …Read More >

Resource Type: Article, Blog, Case Study
Resource Topic: Discovery Chemistry, Small Molecules, Targeted Protein Degradation

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DEL Insight: Novel Applications with the Bifunctional Linker of DNA-encoded Molecules

Due to the special configuration of the DNA encoded library (DEL), each DEL molecule carries a DNA sequence encoding its identity through a bifunctional linker. The linkers that are considered “redundant” and “troublesome” in traditional drug discovery actually offer innate advantages in many application scenarios. In this article, we review how to utilize DNA-encoded libraries …Read More >

Resource Type: Article, Blog
Resource Topic: DNA-Encoded Library (DEL), Hit Finding, Small Molecules

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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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Empowering Small Molecule Drug Discovery by Automatic DEL Screening

In this webinar, our expert speakers showcase our automatic DNA-encoded library (DEL) screening device, DELman. DNA-encoded library technology has proven to be a powerful tool for drug discovery. There are now several DEL-derived candidates in clinical stage. DEL enables researchers to explore vast chemical space with millions to billions of compounds. With DELman and other …Read More >

Resource Type: Webinar
Resource Topic: DNA-Encoded Library (DEL), Hit Finding, Small Molecules

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Resource Topics
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