Results 21 to 30 of about 504,547 (295)

Context matters: E3 ligase–ligand pairing strategies for optimized PROTAC performance

Protein & Cell
PROTACs (proteolysis-targeting chimeras) offer a revolutionary strategy to degrade proteins previously considered “undruggable.” While the importance of the target protein ligand and linker is well-established, the strategic selection of an E3 ubiquitin ...
Lu-Yao Yin, Peng-Cheng Shu, Xiao-Zhong Peng   +2 more
semanticscholar   +4 more sources

Evaluation of the binding affinity of E3 ubiquitin ligase ligands by cellular target engagement and in-cell ELISA assay

STAR Protocols, 2021
Summary: The discovery of potent cell-permeable E3 ubiquitin ligase ligands can significantly facilitate the development of proteolysis targeting chimeras (PROTACs).
Ka Yang, Yaxian Zhou, Brett L. Roberts, Xueqing Nie, Weiping Tang   +4 more
doaj   +1 more source

PROTACs: A novel strategy for cancer drug discovery and development

MedComm, 2023
Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an ...
Xin Han, Yi Sun
doaj   +1 more source

Mind Bomb-2 Is an E3 Ligase for Notch Ligand [PDF]

Journal of Biological Chemistry, 2005
The zebrafish gene, mind bomb (mib), encodes a protein that positively regulates of the Delta-mediated Notch signaling. It interacts with the intracellular domain of Delta to promote its ubiquitination and endocytosis. In our search for the mouse homologue of zebrafish mind bomb, we cloned two homologues in the mouse genome: a mouse orthologue (mouse ...
Bon-Kyoung, Koo, Ki-Jun, Yoon, Kyeong-Won, Yoo, Hyoung-Soo, Lim, Ran, Song, Ju-Hoon, So, Cheol-Hee, Kim, Young-Yun, Kong   +7 more
openaire   +2 more sources

Exploration of Aberrant E3 Ligases Implicated in Alzheimer’s Disease and Development of Chemical Tools to Modulate Their Function

Frontiers in Cellular Neuroscience, 2021
The Ubiquitin Proteasome System (UPS) is responsible for the degradation of misfolded or aggregated proteins via a multistep ATP-dependent proteolytic mechanism. This process involves a cascade of ubiquitin (Ub) transfer steps from E1 to E2 to E3 ligase.
Frances M. Potjewyd, Alison D. Axtman
doaj   +1 more source

Investigation of E3 ligase ligands for targeted protein degradation

Targeted protein degradation (TPD) is a therapeutic strategy that harnesses the cell’s protein quality control machinery to selectively remove disease-relevant proteins.
Kabir, Farah
core   +4 more sources

Replacing the phthalimide core in thalidomide with benzotriazole

Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide ...
Mikhail Krasavin, Andrey Bubyrev, Alexander Kazantsev, Christopher Heim, Samuel Maiwald, Daniil Zhukovsky, Dmitry Dar’in, Marcus D. Hartmann, Alexander Bunev   +8 more
doaj   +1 more source

Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1alpha (HIF-1alpha) Stabilizers [PDF]

, 2023
Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation to hypoxia in humans. HIF-1α protein level and activity is tightly regulated by the ubiquitin E3 ligase von Hippel-Lindau (VHL). Here, we performed a structure-
Izidor , Sosic, Lan , Phuong Vu, Ryan, Casement, Nika, Strasek, Alesa , Bricelj, Gregor, Schnakenburg, Michael, Gutschow, Adam, Bond, Alessio, Ciulli, Claudia, Diehl, Andrej , Perdih, Christian , Steinebach   +11 more
core   +2 more sources

Synthesis of novel glutarimide ligands for the E3 ligase substrate receptor Cereblon (CRBN): Investigation of their binding mode and antiproliferative effects against myeloma cell lines.

European journal of medicinal chemistry, 2023
To expand the chemical toolkit for targeted protein degradation, we report the generation of a new series of non-thalidomide Cereblon (CRBN) ligands. Readily available 2-methylidene glutarimide was converted to a series of 2-((hetero)aryl(methyl))thio ...
M. Krasavin, M. Adamchik, A. Bubyrev, C. Heim, Samuel A. Maiwald, Daniil Zhukovsky, P. Zhmurov, A. Bunev, M. Hartmann   +8 more
semanticscholar   +1 more source

Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype

Nature Communications, 2023
Targeted proteasomal and autophagic protein degradation, often employing bifunctional modalities, is a new paradigm for modulation of protein function.
Gang Xue, Jianing Xie, Matthias Hinterndorfer, Marko Cigler, Lara Dötsch, Hana Imrichova, Philipp Lampe, Xiufen Cheng, Soheila Rezaei Adariani, Georg E. Winter, Herbert Waldmann   +10 more
doaj   +1 more source