Results 81 to 90 of about 644,957 (254)

Enhancing structure-based virtual screening of MDM2–p53 inhibitors: a benchmark of machine learning vs. traditional docking scoring functions

Frontiers in Drug Discovery
The interaction between p53 and MDM2 represents a key therapeutic target in several cancers where MDM2 overexpression suppresses p53 activity. Despite extensive research, the discovery of potent and selective MDM2 inhibitors remains challenging ...
Marcia Yineth Castillo Tarazona, Gian Pietro Miscione   +1 more
doaj   +1 more source

Enhanced 5-FU-mediated activation of p53-dependent nucleolar stress by MDM2/4 peptide inhibitors in colon cancer cells

, 2022
Recent evidence suggest that the p53-dependent nucleolar stress induced by some anticancer drugs, such as 5-Fluorouracil (5-FU), might not be sufficient to produce cell cycle arrest and/or apoptosis, given the hyperactivation of MDM2 and MDM4, main ...
Giulia Russo, Annalisa Pecoraro, Daniele Bravoco, Chiara Brignola, Annapina Russo., Francesco Merlino, Valeria La Pietra   +6 more
core  

TP53 Loss Elevates NF‐κB‐IFN‐β‐MHC‐Ia Signaling to Promote NK Cell Resistance in Osteosarcoma

Advanced Science, EarlyView.
TP53 loss in a transforming or osteosarcoma cell promotes cytosolic DNA accumulation, activating NF‐κB‐dependent IFN‐β production. Autocrine IFN‐β signaling increases cell‐surface HLA‐Ia expression, strengthens inhibitory KIR signaling in natural killer cells, and thereby enables the affected cell to evade NK cell‐mediated cytotoxicity.
Guihui Qin, Cheung Kwan Yeung, Ye Yi, Dejin Zheng, Miaoman Ye, Chi‐Chong Chio, Jinjie Wu, Siyi Fu, Chu‐Xia Deng, Ren‐He Xu   +9 more
wiley   +1 more source

Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy

Frontiers in Pharmacology, 2018
The β-catenin and MDM2 oncoproteins are overexpressed and constitutively activated in human pancreatic cancer and contribute to its initiation, progression, and metastasis.
Jiang-Jiang Qin, Wei Wang, Wei Wang, Xin Li, Hemantkumar Deokar, John K. Buolamwini, Ruiwen Zhang, Ruiwen Zhang   +7 more
doaj   +1 more source

Transient Protein States in Designing Inhibitors of the MDM2-p53 Interaction [PDF]

, 2013
Reactivation of p53 by release of the functional protein from its inhibition by MDM2 provides an efficient, nongenotoxic approach to a wide variety of cancers.
Bista, Michał, Bista, M., Domling, A., Surmiak, Ewa, Holak, Tadeusz, Popowicz, Grzegorz M, Khoury, K., Kowalska, K., Holak, Tad A, Popowicz, G.M., Kowalska, Kaja, Holak, T., Arciniega, Marcelino, Wolf, Siglinde, Huang, Yijun, Domling, Alexander, Huang, Y., Popowicz, G., Wrona, Ewa, Popowicz, Grzegorz M., Bista, Michal, Arciniega, M., Wolf, S., Holak, Tad A., Holak, T.A., Khoury, Kareem, Wrona, E.   +26 more
core   +2 more sources

A Multistrategy AI‐Assisted Consensus Screening Pipeline for Discovery of Candidate p53 Monomer Binders

Advanced Intelligent Discovery, EarlyView.
An ultra‐fast small‐sample AI consensus pipeline combines co‐folding and docking to target structure‐lacking p53 monomers. Its optimal mini‐protein binder shows robust interfacial affinity and promising druggability, supplying unprecedented antitumor p53 templates.
Ningyao Li, Xueyi Liu, Qiuyue Li, Chengfeng Yue, Xin Li, Yugang Huang, Xin Deng, Junfei Zhang, Xue Liang, Guodong Ye   +9 more
wiley   +1 more source

MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis

npj Precision Oncology
Murine double minute 2 (MDM2) inhibitors have shown promising activity in TP53-wild type tumors and are under active investigation across a spectrum of malignancies.
Vishesh Khanna, Gohar Eslami, Rochelle Reyes, Robert Diep, Sebastian Fernandez-Pol, Henning Stehr, Carlos Jose Suarez, Harlan Pinto, James M. Ford, Tian Yi Zhang, Christopher T. Chen   +10 more
doaj   +1 more source

Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides. [PDF]

, 2019
Herein, we describe the development of a novel staple with an electrophilic warhead to enable the generation of stapled peptide covalent inhibitors of the p53-MDM2 protein-protein interaction (PPI).

core   +2 more sources

MDM2-mediated degradation of p14ARF: a novel mechanism to control ARF levels in cancer cells.

PLoS ONE, 2015
We here show a new relationship between the human p14ARF oncosuppressor and the MDM2 oncoprotein. MDM2 overexpression in various cancer cell lines causes p14ARF reduction inducing its degradation through the proteasome.
Maria Vivo, Maria Matarese, Maria Sepe, Rosaria Di Martino, Luisa Festa, Viola Calabrò, Girolama La Mantia, Alessandra Pollice   +7 more
doaj   +1 more source

Not all NTRK fusions in mesenchymal neoplasia are driver events: implications on classification and targeted therapy. [PDF]

J Pathol Clin Res
Abstract NTRK fusions drive the pathogenesis of a distinctive group of mesenchymal neoplasms with significant impact on classification and targeted therapy. However, unexpected NTRK fusions have been reported in other sarcoma entities, raising uncertainty over their specificity and clinical management.
Yakoub MA, Sukhadia P, Saoud C, Hameed M, Antonescu CR.   +4 more
europepmc   +2 more sources