Strategies for designing proteolysis targeting chimaeras (PROTACs)
Sign Up to like & getrecommendations! Published in 2022 at "Medicinal Research Reviews"
DOI: 10.1002/med.21877
Abstract: Proteolysis targeting chimaeras (PROTACs) is a cutting edge and rapidly growing technique for new drug discovery and development. Currently, the largest challenge in the molecular design and drug development of PROTACs is efficient identification of… read more here.
Keywords: protacs; chimaeras protacs; proteolysis targeting; targeting chimaeras ... See more keywords
Optimising proteolysis-targeting chimeras (PROTACs) for oral drug delivery: a drug metabolism and pharmacokinetics perspective.
Sign Up to like & getrecommendations! Published in 2020 at "Drug discovery today"
DOI: 10.1016/j.drudis.2020.07.013
Abstract: Proteolysis-targeting chimeras (PROTACs) are an emerging therapeutic modality with the potential to open target space not accessible to conventional small molecules via a degradation-based mechanism; however, their bifunctional nature can result in physicochemical properties that… read more here.
Keywords: metabolism pharmacokinetics; targeting chimeras; drug; proteolysis targeting ... See more keywords
Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC).
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112800
Abstract: Histone deacetylases (HDACs) play important roles in inflammatory diseases like asthma and chronic obstructive pulmonary disease (COPD). Unravelling of and interfering with the functions of specific isoenzymes contributing to inflammation provides opportunities for drug development.… read more here.
Keywords: proteolysis targeting; protac; degradation; histone deacetylases ... See more keywords
Importance of Three-Body Problems and Protein-Protein Interactions in Proteolysis-Targeting Chimera Modeling: Insights from Molecular Dynamics Simulations
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DOI: 10.1021/acs.jcim.1c01150
Abstract: Proteolysis-targeting chimeras (PROTACs) are a class of bifunctional molecules that can induce the ubiquitin degradation of its target protein by hijacking the E3 ligase to form a target protein-PROTAC-E3 ligase ternary complex. Its underlying principle… read more here.
Keywords: three body; protein protein; molecular dynamics; protein interactions ... See more keywords
Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications
Sign Up to like & getrecommendations! Published in 2020 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.0c00793
Abstract: Hetero-bifunctional PROteolysis TArgeting Chimeras (PROTACs) represent a new emerging class of small molecules designed to induce polyubiquitylation and proteasomal-dependent degradation of a target protein. Despite the increasing number of publications about the synthesis, biological evaluation,… read more here.
Keywords: understanding metabolism; metabolism; targeting chimeras; proteolysis targeting ... See more keywords
Unraveling the Role of Linker Design in Proteolysis Targeting Chimeras.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c00482
Abstract: A current bottleneck in the development of proteolysis targeting chimeras (PROTACs) is the empirical nature of linker length structure-activity relationships (SARs). A multidisciplinary approach to alleviate the bottleneck is detailed here. First, we examine four… read more here.
Keywords: linker design; targeting chimeras; chemistry; proteolysis targeting ... See more keywords
Novel CRBN-Recruiting Proteolysis-Targeting Chimeras as Degraders of Stimulator of Interferon Genes with In Vivo Anti-Inflammatory Efficacy.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01948
Abstract: The activation of the cyclic GMP-AMP synthase-stimulator of interferon gene (STING) pathway has been associated with the pathogenesis of many autoimmune and inflammatory disorders, and small molecules targeting STING have emerged as a new therapeutic… read more here.
Keywords: crbn; stimulator interferon; anti inflammatory; proteolysis targeting ... See more keywords
Rational Design for Nitroreductase (NTR)-Responsive Proteolysis Targeting Chimeras (PROTACs) Selectively Targeting Tumor Tissues.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c02221
Abstract: The catalytic properties of proteolysis targeting chimeras (PROTACs) may lead to uncontrolled off-tissue target degradation that causes potential toxicity, limiting their clinical applications. The precise control of this technology in a tissue-selective manner can minimize… read more here.
Keywords: ntr responsive; chimeras protacs; proteolysis targeting; tumor tissues ... See more keywords
Beyond Proteolysis-Targeting Chimeric Molecules: Designing Heterobifunctional Molecules Based on Functional Effectors.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00316
Abstract: In recent years, with the successful development of proteolysis-targeting chimeric molecules (PROTACs), the potential of heterobifunctional molecules to contribute to reenvisioning drug design, especially small-molecule drugs, has been increasingly recognized. Inspired by PROTACs, diverse heterobifunctional… read more here.
Keywords: targeting chimeric; heterobifunctional molecules; chimeric molecules; proteolysis targeting ... See more keywords
Exploring Degradation of Mutant and Wild-Type Epidermal Growth Factor Receptors Induced by Proteolysis-Targeting Chimeras.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00345
Abstract: Several epidermal growth factor receptor (EGFR) proteolysis-targeting chimeras (PROTACs), including MS39 and MS154 developed by us, have been reported to effectively degrade the mutant but not the wild-type (WT) EGFR. However, the mechanism underlying the… read more here.
Keywords: epidermal growth; growth factor; mutant wild; egfr ... See more keywords
Novel Allosteric Inhibitor-Derived AKT Proteolysis Targeting Chimeras (PROTACs) Enable Potent and Selective AKT Degradation in KRAS/BRAF Mutant Cells.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01454
Abstract: AKT is an important target for cancer therapeutics. Significant advancements have been made in developing ATP-competitive and allosteric AKT inhibitors. Recently, several AKT proteolysis targeting chimeras (PROTACs) derived from ATP-competitive AKT inhibitors have been reported,… read more here.
Keywords: kras braf; akt proteolysis; proteolysis targeting; akt ... See more keywords