Results 191 to 200 of about 7,268 (227)

p53–MDM2 and MDMX Antagonists

2014
Abstract The protein–protein interaction of the oncogene mouse double minute 2 (MDM2) and the transcription factor tumor-suppressor p53 is an emerging target in oncology, and prove of concept for their druggability has been established by the discovery of Nutlin.
Neochoritis, Dinos, Estrada-Ortiz, Natalia, Khoury, Kareem, Dömling, Alex   +3 more
openaire   +2 more sources

MDMX Stability Is Regulated by p53-Induced Caspase Cleavage in NIH3T3 Mouse Fibroblasts

Oncogene, 2002
MDMX is a p53 binding protein, which shares a high degree of homology with MDM2, a negative regulator of the tumor suppressor p53. MDMX has been shown to counteract MDM2-dependent p53 degradation and to stabilize p53 in its inactive form.
Aart Jochemsen, Francesca Mancini, Fabiola Moretti   +2 more
exaly   +2 more sources

A Dual-Specificity d-Peptide Antagonist of MDM2 and MDMX for Antitumor Immunotherapy.

Journal of Medicinal Chemistry
Designing metabolically stable peptides to target interactions of the tumor suppressor protein p53 with the two oncogenic proteins MDM2 and MDMX represents an attractive approach to harvesting "high-hanging fruits" often inaccessible to traditional ...
Chong-Bing Liao, Jin Yan, W. Tolbert, Xi-Shan Chen, M. Pazgier, Wei-Yue Lu, Chang-You Zhan, Wu-Yuan Lu   +7 more
semanticscholar   +1 more source

Medicinal Chemistry Strategies to Disrupt the p53–MDM2/MDMX Interaction

Medicinal Research Reviews, 2016
The growth inhibitory activity of p53 tumor suppressor is tightly regulated by interaction with two negative regulatory proteins, murine double minute 2 (MDM2) and X (MDMX), which are overexpressed in about half of all human tumors.
Agostinho Lemos, Andreia Palmeira, Madalena Maria de Magalhães Pinto   +2 more
exaly   +2 more sources

Regulation of p63 Function by Mdm2 and MdmX

DNA and Cell Biology, 2001
p63, a p53-related protein, has been shown to activate p53-responsive genes and induce apoptosis in certain cell types. In this study, we examined the effects of Mdm2 and MdmX proteins on p63 transactivation, apoptosis, and protein levels. The isoforms of p63 most structurally similar to p53, p63gamma (p51A) and p63alpha (p51B), were chosen for study ...
M, Kadakia, C, Slader, S J, Berberich
openaire   +2 more sources

Review: MDMX plays a central role in leukemic transformation and may be a promising target for leukemia prevention strategies.

Experimental Hematology, 2023
Acute myeloid leukemia (AML) is a fatal disease resulting from preleukemic hematopoietic conditions including asymptomatic clonal hematopoiesis. The accumulation of genetic changes is one of the causes of leukemic transformation.
K. Ueda
semanticscholar   +1 more source

Mdmx as an essential regulator of p53 activity

Biochemical and Biophysical Research Communications, 2005
The murine double minute 2 (Mdm2) is a critical negative regulator of the p53 tumor suppressor. Almost 10 years ago, a search for new p53-interactors revealed the existence of an Mdm2-structurally related protein, Mdmx (or Mdm4). Since then a large body of biochemical data has accumulated on the functions of Mdmx, often leading to conflicting molecular
Jean-Christophe, Marine, Aart G, Jochemsen   +1 more
openaire   +2 more sources

MDM2 and MDMX in Cancer and Development

2011
The p53 tumor suppressor pathway is active in cells that are subjected to stress and/or damaged, where it promotes cell cycle arrest or apoptosis. In contrast, in normal cells that are not exposed to stress signals and in tumor cells p53 is tightly kept in check or completely silenced.
openaire   +2 more sources

Design, Synthesis, and Biological Evaluation of Lysine-Stapled Peptide Inhibitors of p53-MDM2/MDMX Interactions with Potent Antitumor Activity In Vivo.

Journal of Medicinal Chemistry
We introduce novel lysine-stapled peptide inhibitors targeting p53-MDM2/MDMX interactions. Leveraging the model peptides pDI (LTFEHYWAQLTS) and PMI-M3 (LTFLEYWAQLMQ) as starting points, a series of lysine-stapled analogues were designed and synthesized ...
Lei Xu, Xin-Yao Fan, Yi He, Xue-Feng Xia, Jin-Qiang Zhang   +4 more
semanticscholar   +1 more source

MDM2/MDMX inhibitor peptide: WO2008106507

Expert Opinion on Therapeutic Patents, 2009
The evidence that some human cancers show wild-type p53 and overexpressed levels of MDM2 and/or MDMX has fueled the search for new therapeutic agents that could rescue p53 from the inhibition of MDM2 and MDMX. Recent data, suggesting a distinct and complementary mode of action of MDM2 and MDMX in the regulation of the pro-apoptotic activity of p53 ...
MACCHIARULO, Antonio, PELLICCIARI, Roberto   +1 more
openaire   +3 more sources