Results 11 to 20 of about 124,194 (317)

Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator [PDF]

Cancer Discovery
Rezatapopt restores tumor suppressor function to p53Y220C by correcting its conformation, reactivating transcriptional programs, and inducing antitumor effects in preclinical models and ongoing clinical trials.
Benjamin D Greenbaum, Shunbin Xiong, Guillermina Lozano   +2 more
exaly   +3 more sources

Discovery of Rezatapopt (PC14586), a First-in-Class, Small-Molecule Reactivator of p53 Y220C Mutant in Development [PDF]

ACS Medicinal Chemistry Letters
p53 is a potent transcription factor that is crucial in regulating cellular responses to stress. Mutations in the TP53 gene are found in >50% of human cancers, predominantly occurring in the DNA-binding domain (amino acids 94–292).
Vu BT, Dominique R, Fahr BJ, Li HH, Fry DC, Xu L, Yang H, Puzio-Kuter A, Good A, Liu B, Huang KS, Tanaka N, Davis TW, Dumble ML.   +13 more
exaly   +3 more sources

AI-powered discovery of a novel p53-Y220C reactivator

Frontiers in Oncology, 2023
IntroductionThe p53-Y220C mutation is one of the most common mutations that play a major role in cancer progression.MethodsIn this study, we applied artificial intelligence (AI)-powered virtual screening to identify small-molecule compounds that ...
Shan Zhou, Dafei Chai, Xu Wang, Praveen Neeli, Xinfang Yu, Aram Davtyan, Ken Young, Yong Li   +7 more
doaj   +2 more sources

APR-246—The Mutant TP53 Reactivator—Increases the Effectiveness of Berberine and Modified Berberines to Inhibit the Proliferation of Pancreatic Cancer Cells

Biomolecules, 2022
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. In ~75% of PDAC, the tumor suppressor TP53 gene is mutated. Novel approaches to treat cancer involve compounds called mutant TP53 reactivators.
James Andrew McCubrey, Stephen L. Abrams, Linda S. Steelman, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Paolo Lombardi, Agnieszka Gizak, Przemysław Duda   +8 more
doaj   +2 more sources

Effects of the Mutant TP53 Reactivator APR-246 on Therapeutic Sensitivity of Pancreatic Cancer Cells in the Presence and Absence of WT-TP53

Cells, 2022
The TP53 tumor suppressor is mutated in ~75% of pancreatic cancers. The mutant TP53 protein in pancreatic ductal adenocarcinomas (PDAC) promotes tumor growth and metastasis.
Stephen L. Abrams, Przemysław Duda, Shaw M. Akula, Linda S. Steelman, Matilde L. Follo, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Giuseppe Montalto, Maria Rita Emma, Melchiorre Cervello, Dariusz Rakus, Agnieszka Gizak, James A. McCubrey   +13 more
doaj   +2 more sources

Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach

Scientific Reports, 2021
Nerve agents have experienced a resurgence in recent times with their use against civilian targets during the attacks in Syria (2012), the poisoning of Sergei and Yulia Skripal in the United Kingdom (2018) and Alexei Navalny in Russia (2020), strongly ...
Brian J. Bennion, Michael A. Malfatti, Nicholas A. Be, Heather A. Enright, Saphon Hok, C. Linn Cadieux, Timothy S. Carpenter, Victoria Lao, Edward A. Kuhn, M. Windy McNerney, Felice C. Lightstone, Tuan H. Nguyen, Carlos A. Valdez   +12 more
doaj   +2 more sources

Molecular Modeling and In Vitro Studies of a Neutral Oxime as a Potential Reactivator for Acetylcholinesterase Inhibited by Paraoxon

Molecules, 2018
The present work aimed to compare the small, neutral and monoaromatic oxime, isatin-3-oxime (isatin-O), to the commercial ones, pralidoxime (2-PAM) and obidoxime, in a search for a new potential reactivator for acetylcholinesterase (AChE) inhibited by ...
Reuel L. de Paula, Joyce S. F. D. de Almeida, Samir F. A. Cavalcante, Arlan S. Gonçalves, Alessandro B. C. Simas, Tanos C. C. Franca, Martin Valis, Kamil Kuca, Eugenie Nepovimova, José M. Granjeiro   +9 more
doaj   +2 more sources

Targeted Synthesis of 1-(4-Hydroxyiminomethylpyridinium)-3-pyridiniumpropane Dibromide – A New Nerve Agent Reactivator

Molecules, 2007
Preparation of 1-(4-hydroxy-iminomethylpyridinium)-3-pyridiniumpropane dibromide is described. This compound represents a new acetylcholinesterase (AChE) reactivator, which has no substituents on the second pyridinium ring as found in other commonly used
Jan Marek, Martina Hrabinova, Petr Stodulka, Daniel Jun, Martin Paar, Kamil Musilek, Kamil Kuca   +6 more
doaj   +2 more sources

Structure of HI-6*sarin-acetylcholinesterase determined by X-ray crystallography and molecular dynamics simulation: reactivator mechanism and design. [PDF]

PLoS ONE, 2009
Organophosphonates such as isopropyl metylphosphonofluoridate (sarin) are extremely toxic as they phosphonylate the catalytic serine residue of acetylcholinesterase (AChE), an enzyme essential to humans and other species.
Fredrik Ekström, Andreas Hörnberg, Elisabet Artursson, Lars-Gunnar Hammarström, Gunter Schneider, Yuan-Ping Pang   +5 more
doaj   +2 more sources

Efficacy Assessment of an Uncharged Reactivator of NOP-Inhibited Acetylcholinesterase Based on Tetrahydroacridine Pyridine-Aldoxime Hybrid in Mouse Compared to Pralidoxime

Biomolecules, 2020
(1) Background: Human exposure to organophosphorus compounds employed as pesticides or as chemical warfare agents induces deleterious effects due to cholinesterase inhibition. One therapeutic approach is the reactivation of inhibited acetylcholinesterase
André-Guilhem Calas, Anne-Sophie Hanak, Nina Jaffré, Aurélie Nervo, José Dias, Catherine Rousseau, Charlotte Courageux, Xavier Brazzolotto, Pascal Villa, Adeline Obrecht, Jean-François Goossens, Christophe Landry, Johan Hachani, Fabien Gosselet, Marie-Pierre Dehouck, Jagadeesh Yerri, Maria Kliachyna, Rachid Baati, Florian Nachon   +18 more
doaj   +2 more sources