BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design [PDF]
, 2019 Targeting subunits of BAF/PBAF chromatin remodeling complexes has been proposed as an approach to exploit cancer vulnerabilities. Here, we develop proteolysis targeting chimera (PROTAC) degraders of the BAF ATPase subunits SMARCA2 and SMARCA4 using a ...
Arnhof, Heribert +36 more
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Recognition of substrate degrons by E3 ubiquitin ligases and modulation by small-molecule mimicry strategies [PDF]
, 2017 The ubiquitin-proteasome system is a master regulator of protein homeostasis, by which proteins are initially targeted for poly-ubiquitination by E3 ligases and then degraded into short peptides by the proteasome.
Alessio Ciulli +80 more
core +2 more sources
Applying antibodies inside cells: Principles and recent advances in neurobiology, virology and oncology [PDF]
, 2020 To interfere with cell function, many scientists rely on methods that target DNA or RNA due to the ease with which they can be applied. Proteins are usually the final executors of function but are targeted only indirectly by these methods.
Marschall, Andrea +4 more
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Protacs for Treatment of Cancer [PDF]
Pediatric Research, 2010 Protein degradation is the cell's mechanism of eliminating misfolded or unwanted proteins. The pathway by which proteins are degraded occurs through the ubiquitin-proteasome system. Ubiquitin is a small 9-kD (kDa) protein that is attached to proteins. A minimum of four ubiquitins are required for proteins to be recognized by the degradation machinery ...
openaire +2 more sources
PROTACs– a game-changing technology [PDF]
Expert Opinion on Drug Discovery, 2019 Introduction: Proteolysis - targeting chimeras (PROTACs) have emerged as a new modality with the potential to revolutionize drug discovery. PROTACs are heterobifunctional molecules comprising of a ligand targeting a protein of interest, a ligand targeting an E3 ligase and a connecting linker.
Konstantinidou, Markella +7 more
openaire +2 more sources
Tackling Drug Resistance in EGFR Exon 20 Insertion Mutant Lung Cancer
Pharmacogenomics and Personalized Medicine, 2021 Laura Pacini,* Andrew D Jenks,* Simon Vyse,* Christopher P Wilding, Amani Arthur, Paul H Huang Division of Molecular Pathology, The Institute of Cancer Research, London, UK*These authors contributed equally to this workCorrespondence: Paul H ...
Pacini L +5 more
doaj
Light-Activating PROTACs in Cancer: Chemical Design, Challenges, and Applications
Applied Sciences, 2022 Nonselective cell damage remains a significant limitation of radiation therapies in cancer. Decades of successful integration of radiation therapies with other medicinal chemistry strategies significantly improved therapeutic benefits in cancer ...
Arvind Negi +2 more
doaj +1 more source
Selective small molecule induced degradation of the BET bromodomain protein BRD4 [PDF]
, 2015 The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1.
Alessio Ciulli +39 more
core +5 more sources
3-Fluoro-4-hydroxyprolines:Synthesis, conformational analysis and stereoselective recognition by the VHL E3 ubiquitin ligase for targeted protein degradation [PDF]
, 2018 Hydroxylation and fluorination of proline alters the pyrrolidine ring pucker and the trans:cis amide bond ratio in a stereochemistry-dependent fashion, affecting molecular recognition of proline-containing molecules by biological systems.
Castro, Guilherme +10 more
core +8 more sources
Cereblon-Recruiting PROTACs: Will New Drugs Have to Face Old Challenges?
Pharmaceutics, 2023 The classical low-molecular-weight drugs are designed to bind with high affinity to the biological targets endowed with receptor or enzymatic activity, and inhibit their function.
Marcin Cieślak, Marta Słowianek
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