degradation mechanism of small molecule

Degradation Mechanism of Small Molecule-Based Organic

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Degradation mechanisms in small-molecule and polymer

Oct 01, 2010 · Degradation in organic light-emitting diodes (OLEDs) is a complex problem. Depending upon the materials and the device architectures used, the degradation mechanism can be very different. In this Progress Report, using examples in both small molecule and polymer OLEDs, the different degradation mechanisms in two types of devices are examined. From Screening to Targeted Degradation:Strategies for the Jan 16, 2020 · Thus, novel strategies to find small-molecule ligands to target these difficult to drug PPIs could greatly impact drug discovery, especially for those with well-validated mechanisms of action. A high-value PPI target that has been clinically validated and has human genetics to support its role in the regulation of LDL and coronary heart disease

Frontiers Targeted Protein Degradation by Chimeric Small

  • Modalities of Recent Drug DevelopmentClassification of Degrader MoleculesDevelopment of Chimeric Degrader MoleculesFeatures of The Chimeric Degrader MoleculesChimeric Degrader Molecules as Probes to Understand The Ubiquitin CodeConclusionFundingConflict of InterestTargeted Protein Degradation by Small Molecules Annual Protein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. Whereas therapeutics have been developed to disrupt protein homeostasis, more recently identified techniques have been used to repurpose homeostatic networks to effect degradation of disease-relevant proteins. Here, we review recent advances in the use of small molecules Gluing Proteins for Targeted Degradation:Cancer CellJan 11, 2021 · Given the novel degradation mechanism triggered by the polymerization of BCL6, one could ask whether it can be applied more broadly to induce degradation of other proteins. Growing evidence indicates that small molecules can induce hetero-dimerization, homo-dimerization, and further polymerization of proteins (Stanton et al., 2018

    MDM2-Recruiting PROTAC Offers Superior, Synergistic

    Although the number of proteins effectively targeted for posttranslational degradation by PROTAC has grown steadily, the number of E3 ligases successfully exploited to accomplish this has been limited to the few for which small-molecule ligands have been discovered. Although the E3 ligase MDM2 is bound by the nutlin class of small-molecule ligands, there are few nutlin-based PROTAC. Proteolysis-targeting chimera (PROTAC) for targeted May 13, 2020 · Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to

    Small Molecule T315 Promotes Casitas B-Lineage Lymphoma

    Apr 01, 2016 · OBJECTIVES:To evaluate the effect of small molecule T315 on EGFR degradation and its therapeutic efficacy in vitro and in vivo. METHODS:Lung adenocarcinoma cells were treated with T315, and cell proliferation and apoptotic proportion were determined by the CellTiter 96 AQueous MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4 Small Molecule-Induced, Selective STAT3 Degradation Leads Nov 13, 2019 · Targeted protein degradation mediated by small molecule degraders represents a new and exciting therapeutic modality to target difficult-to-drug oncogenic proteins including transcription factors. These molecules bind to both the target protein and an E3 ligase, enabling the formation of a ternary complex that leads to ubiquitination and

    Small molecule probes for targeting autophagy Nature

    May 25, 2021 · Autophagy is an essential catabolic cellular degradation process. It is responsible for the degradation of damaged or otherwise dispensable proteins, as well as aggregates 1 and droplets 2, by TRIP12 promotes small-molecule-induced degradation Small-molecule degraders such as proteolysis-targeting chimeras (PROTACs) induce the degradation of neo-substrates by hijacking E3 ubiq-uitin ligases. Although ubiquitylation of endogenous substrates has been extensively studied, the mecha-nism underlying forced degradation of neo-substrates is less well understood. We found that the ubiquitin

    Targeted protein degradation and drug discovery IRB

    Targeted protein degradation (TPD) holds the promise to overcome these limitations. TPD is based on small-molecule drugs, generally called degraders, which induce proximity between a ubiquitin E3 ligase and a target protein of interest (neosubstrate). As a result, the target protein is ubiquitinated and then degraded by the proteasome.Small-molecule-induced polymerization triggers degradation Here we report an alternative mechanism of targeted protein degradation, in which a small molecule induces the highly specific, reversible polymerization of a target protein, followed by its sequestration into cellular foci and subsequent degradation. BI-3802 is a small molecule that binds to the Broad-complex, Tramtrack and Bric-à-brac (BTB) domain of the oncogenic transcription factor B cell lymphoma 6 (BCL6) and leads to the proteasomal degradation