Results 51 to 60 of about 4,302 (134)

Cereblon deficiency ameliorates carbon tetrachloride-induced acute hepatotoxicity in HepG2 cells by suppressing MAPK-mediated apoptosis

Frontiers in Immunology
The liver is vulnerable to various hepatotoxins, including carbon tetrachloride (CCl4), which induces oxidative stress and apoptosis by producing reactive oxygen species (ROS) and activating the mitogen-activated protein kinase (MAPK) pathway.
Seo Young Choi, Parkyong Song, Ji Sun Hwang, You Kyeong Lee, Mi Song Shin, Hong-Joo Son, Yu-Jin Kim, Wanil Kim, Kwang Min Lee   +8 more
doaj   +1 more source

Tubulin Resists Degradation by Cereblon-Recruiting PROTACs

Cells, 2020
Dysregulation of microtubules and tubulin homeostasis has been linked to developmental disorders, neurodegenerative diseases, and cancer. In general, both microtubule-stabilizing and destabilizing agents have been powerful tools for studies of ...
Ivana Gasic, Brian J. Groendyke, Radosław P. Nowak, J. Christine Yuan, Joann Kalabathula, Eric S. Fischer, Nathanael S. Gray, Timothy J. Mitchison   +7 more
doaj   +1 more source

Pharmacological degradation of ATR induces antiproliferative DNA replication stress in leukemic cells

Molecular Oncology
Mammalian cells replicate ~ 3 × 109 base pairs per cell cycle. One of the key molecules that slows down the cell cycle and prevents excessive DNA damage upon DNA replication stress is the checkpoint kinase ataxia‐telangiectasia‐and‐RAD3‐related (ATR ...
Anita G. Kansy, Ramy Ashry, Al‐Hassan M. Mustafa, Abdallah M. Alfayomy, Markus P. Radsak, Yanira Zeyn, Matthias Bros, Wolfgang Sippl, Oliver H. Krämer   +8 more
doaj   +1 more source

Lenalidomide maintenance after initial immunochemotherapy in chronic lymphocytic leukaemia—Final analysis of the international phase III CLL6 RESIDUUM study of the ALLG and FILO groups

British Journal of Haematology, EarlyView.
Summary Most patients treated for chronic lymphocytic leukaemia (CLL) fail to achieve measurable residual disease (MRD) negativity. The role of maintenance with the immunomodulatory drug lenalidomide in these patients is unclear. A randomised multicentre phase III trial (ACTRN12610000060044) was conducted in Australia and France to assess the effect of
Thérèse Aurran‐Schleinitz, Rémi Letestu, Mary Sartor, Stephen Mulligan, Marie C. Béné, Gavin Cull, Dennis Carney, William Renwick, Andrew Grigg, Cecily Forsyth, Gregory Hapgood, Emma Verner, Rosemary Harrup, Pauline Warburton, Kylie Mason, Richard Eek, Wojciech Janowski, Jean Pierre Vilque, Maya Latimer, Laurent Voillat, Sophie De Guibert, Bernard Drenou, Robert Blum, Caroline Dartigeas, Lachlan Hayes, Nicolas Daguindau, Mourad Tiab, Véronique Leblond, Andrew Shearer, Masa Lasica, Pierre Morel, Bohrane Slama, Anne Banos, Annie Brion, Emmanuelle Ferrant, Jessica Michel, Cécile Tomowiak, Edward Morris, Hanlon Sia, Kelly Kratzing, Belinda E. Butcher, Abdelmalek Dahmani, Stephen Robert Larsen, Piers Blombery, Florence Cymbalista, David J. Gottlieb   +45 more
wiley   +1 more source

Targeting bromodomain-containing protein 4 (BRD4) inhibits MYC expression in colorectal cancer cells

Neoplasia: An International Journal for Oncology Research, 2019
The transcriptional regulator BRD4 has been shown to be important for the expression of several oncogenes including MYC. Inhibiting of BRD4 has broad antiproliferative activity in different cancer cell types. The small molecule JQ1 blocks the interaction
C. Otto, S. Schmidt, C. Kastner, S. Denk, J. Kettler, N. Müller, C.T. Germer, E. Wolf, P. Gallant, A. Wiegering   +9 more
doaj   +1 more source

Chemoproteomic discovery of a brain‐penetrant, covalent NLRP3 inhibitor that binds a novel allosteric pocket

British Journal of Pharmacology, EarlyView.
NLRP3 is a promising inflammatory target, but existing inhibitors lack diversity and brain penetrance, and none are approved. Using chemoproteomics, we discovered a novel series that binds to Cys463 in a previously uncharacterized pocket. Compounds showed nanomolar potency, brain exposure, and in vivo suppression of IL‐1β, supporting neuroinflammatory ...
Donald C. Rogness, Evelyn P. Sievert, Vincent F. Vartabedian, Steffen M. Bernard, Erick Aitchison, William Tao, Mikaela Lindvall, Jing Qian, Christie L. Eissler, Brian E. Nordin, Benjamin D. Horning, Cian Kingston, Kelsey N. Lamb, Joshua C. Bell, Bingwen Lu, Jonathan Pollock, Jun Shi, Roli Khattri, David S. Weinstein, Matthew P. Patricelli, Brian N. Cook, Gabriel M. Simon   +21 more
wiley   +1 more source

The c‐Src inhibitor eCF506 diminishes opioid tolerance and reduces β‐arrestin2 recruitment

British Journal of Pharmacology, EarlyView.
Morphine activation of μ receptors causes tolerance through c‐Src activation and β‐arrestin2 recruitment. c‐Src inhibition or degradation reduces β‐arrestin2 recruitment, μ receptor endocytosis, while causing receptor upregulation, all likely contributing to reduced morphine tolerance.
Samuel Singleton, Fraser Nunn, Erika Lace, Álvaro Lorente‐Macías, Rachel Toth, Asier Unciti‐Broceta, Tim G. Hales   +6 more
wiley   +1 more source

Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma

Biomolecules
Immunomodulatory imide drugs (IMiDs) play a crucial role in the treatment landscape across various stages of multiple myeloma. Despite their evident efficacy, some patients may exhibit primary resistance to IMiD therapy, and acquired resistance commonly ...
Blaire E. Barton, Matthew K. Collins, Cindy H. Chau, Hyoyoung Choo-Wosoba, David J. Venzon, Christian Steinebach, Kathleen M. Garchitorena, Bhruga Shah, Eric L. Sarin, Michael Gütschow, William D. Figg   +10 more
doaj   +1 more source

Limiting Trial‐and‐Error: Linker‐Based 2D Descriptor Analysis to Support Very Early Proteolysis‐Targeting Chimeras Design

ChemMedChem, Volume 21, Issue 19, 14 October 2026.
Can simple linker descriptors guide PROTAC design? Analysis of matched CRBN‐ and VHL‐recruiting degraders shows that basic 2D linker properties may capture trends linked to degradation efficiency, in vitro ADME and physicochemical properties. A practical approach to reduce trial‐and‐error in early targeted protein degradation programs. Targeted protein
Giulia Apprato, Serena Traversa, Giulia Caron, Giuseppe Ermondi   +3 more
wiley   +1 more source

Paediatric developmental safety and the ICH E11A extrapolation of safety

British Journal of Clinical Pharmacology, EarlyView.
Gilbert J. Burckart, Susan M. Abdel‐Rahman, Gelareh Abulwerdi, Rebecca Racz, Sherbet Samuels, Dionna J. Green, Lynne P. Yao   +6 more
wiley   +1 more source