Knowledge Library

Optimization and Mechanistic Investigations of Novel Allosteric Activators of PKG1α

WuXi AppTec scientists recently contributed to a research article in the Journal of Medicinal Chemistry describing the optimization of a piperidine series of small molecules as novel allosteric activators of PKG1α (a compelling drug target for treatment of cardiovascular diseases).  This study reveals a mechanism of action for these compounds consistent with cGMP-induced activation, including …Read More >

Resource Type: Latest Science Publication
Resource Topic: Cardiovascular & Metabolic Diseases Discovery Chemistry Small Molecules

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Large-scale synthesis of a Notum inhibitor employing a modified Sakai reaction as the key step

WuXi AppTec scientists recently contributed to a research article in the Royal Society of Chemistry describing the large-scale synthesis of a potent and selective inhibitor of Notum carboxylesterase (an enzyme that suppresses Wnt signaling pathways).  By employing a modified Sakai reaction as the key step, a one-pot synthesis of this Notum inhibitor was developed, enabling …Read More >

Resource Type: Latest Science Publication
Resource Topic: Cardiovascular & Metabolic Diseases Discovery Chemistry Liver Diseases Oncology Respiratory Diseases Small Molecules

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Discovery and Structural Characterization of Small Molecule Binders of the Human CTLH E3 Ligase Subunit GID4

Expansion of the E3 ligase toolbox has the potential to dramatically advance the field of targeted protein degradation.  WuXi AppTec scientists recently contributed to a research article in the Journal of Medicinal Chemistry describing the discovery of novel small molecule binders of GID4, a substrate receptor in the human CTLH E3 ligase complex.  Researchers used …Read More >

Resource Type: Latest Science Publication
Resource Topic: DNA-Encoded Library (DEL) Fragment-Based Drug Discovery Targeted Protein Degradation

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KRAS-related Genetically Engineered Cell Lines and In Vivo Models

KRAS mutant proteins that drive cancer development are highly similar in sequence and structure. Direct inhibitors are most likely to bind to the catalytic domain of KRAS. However, recent studies have found that KRAS mutants can also be targeted by heterogeneous sites, to develop covalent inhibitors of KRAS mutants. The discovery of inhibitors that selectively …Read More >

Resource Type: Latest Science Presentation
Resource Topic: Biochemical Assays Biophysical Assays Cell-based Assays Cells and Protein Science Hit Finding Hit-to-Lead Lead Optimization Oncology Small Molecules Tumor Models

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Targeted Protein Degradation

WuXi AppTec utilizes state-of-the-art techniques to support drug discovery teams focused on targeted protein degradation. Our services include a broad range of ligand-finding methods, such as DEL, fragment screening, ASMS, and virtual screening. We provide custom linker design and complex synthesis for new linkers and E3 ligase ligands. To support lead optimization efforts, our platform …Read More >

Resource Type: Brochure Latest Science
Resource Topic: Biochemical Assays Biophysical Assays Cell-based Assays Mass Spectrometry-based Assays Oncology Small Molecules Structural Biology Targeted Protein Degradation

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Ligand Finding and Chemistry Workflows for Targeted Protein Degradation

This webinar will focus on aspects related to PROTAC discovery and chemistry workflows, such as ligand finding strategies, synthesis optimization, and linker design. Successful development of bifunctional molecules requires a deep understanding of multiple processes, including biophysical events which dictate induced proximity and how technologies such as DNA-encoded libraries (DEL) can be leveraged to identify …Read More >

Resource Type: Webinar
Resource Topic: Autoimmune and Inflammatory Diseases Biophysical Assays Cardiovascular & Metabolic Diseases Central Nervous System & Pain Discovery Chemistry DNA-Encoded Library (DEL) Hit Finding Hit-to-Lead Lead Optimization Oncology Small Molecules Structural Biology Target-Specific Assays Targeted Protein Degradation

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Biological Characterization and Development Workflows for Targeted Protein Degradation

This webinar will focus on PROTAC biology workflows, such as in vitro screening assays, in vivo testing, and optimization of DMPK properties. Topics will include the best use of biochemical assays to measure binary/ternary complex formation, cell-based assays to assess target engagement and degradation, strategies for enhancing drug delivery and formulation, and PK/PD evaluation of …Read More >

Resource Type: Webinar
Resource Topic: Autoimmune and Inflammatory Diseases Biochemical Assays Cardiovascular & Metabolic Diseases Cell-based Assays Central Nervous System & Pain Hit-to-Lead in vitro biology in vivo Pharmacology Lead Optimization Oncology Small Molecules Target Identification and Validation Target-Specific Assays Targeted Protein Degradation

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Discovery Newsletter Special New Year Edition 2023

Resource Type: Latest Science Newsletter
Resource Topic: Biophysical Assays Central Nervous System & Pain Discovery Chemistry DNA-Encoded Library (DEL) Hit-to-Lead in silico services Lead Optimization Quantum Mechanics Small Molecules Target Identification and Validation Targeted Protein Degradation

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DNA-encoded chemical libraries

https://www.nature.com/articles/s43586-021-00084-5  Abstract DNA-encoded chemical library (DECL) technology is used by the pharmaceutical industry to discover small molecules capable of modulating biologically relevant targets. DECL synthesis starts with an oligonucleotide that contains a chemical linker moiety, and proceeds through iterative cycles of DNA barcode elongation and chemical synthesis. DECL selections require little protein, minimal assay development …Read More >

Resource Type: Publication
Resource Topic: Discovery Chemistry DNA-Encoded Library (DEL) DRUG DISCOVERY AND INNOVATION Hit Finding Screening Libraries Small Molecules Target Identification and Validation

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