Results 91 to 100 of about 692,269 (276)

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

CD112 Lactylation Drives Dual Immune Evasion From CD8+ T Cells and NK Cells

Advanced Science, EarlyView.
AARS2 functions as an intracellular lactate sensor and lactyltransferase, catalyzing CD112 K412 lactylation to block ubiquitination‐dependent degradation and stabilize CD112. This pathway suppresses CD8+ T‐cell and NK‐cell cytotoxicity, enabling dual immune evasion.
Zhuoshuo Xu, Xinyu Zhang, Fang Dong, Nenghao Shen, Jun Zhou, Zihan Xi, Zhenghao Wu   +6 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

Lactate‐H3K18la‐RPL11 Axis Drives Gemcitabine Resistance in Pancreatic Cancer by Integrating Protein Synthesis and DNA Damage Repair

Advanced Science, EarlyView.
A lactate‐H3K18la epigenetic axis upregulates RPL11 to drive gemcitabine resistance in pancreatic cancer. RPL11 orchestrates chemoresistance through a dual, compartmentalized role: enhancing cytoplasmic protein synthesis via EEF1A1 stabilization and promoting nuclear DNA damage repair by co‐activating PARP14, thus ensuring robust cell survival ...
Lijun Zhao, Jianzhong Cao, Wenyue Liu, Xuyun Li, Haolin Zhang, Xiaofang Zhang, Shiyang Shi, Huilong Yin, Junjie Li, Angang Yang, Rui Zhang   +10 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

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers [PDF]

, 2006
BackgroundThe MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in ...
Johnson, Peter W., White Helen E, Jeremy P Blaydes, Diana M Eccles, White, Helen E., Ellen R Copson, Johnson Peter W, Eccles Diana M, Eccles, Diana M., Helen E White, Robinson, David O., David O Robinson, Peter W Johnson, Blaydes, Jeremy P., Copson, Ellen R., Robinson David O, Copson Ellen R, Blaydes Jeremy P   +17 more
core   +2 more sources

A Living Multi‐Omics PDX Biobank of High‐Risk Sarcomas Reveals ecDNA‐Driven Oncogene Amplification in Osteosarcoma and Enables Preclinical Precision Oncology

Advanced Science, EarlyView.
A living multi‐omics sarcoma PDX biobank is enriched for high‐risk disease and preserves key patient tumor features at histopathological and molecular levels. Integrated profiling reveals ecDNA‐driven oncogene amplification in osteosarcoma and preferential retention of ecDNA during PDX evolution.
Weisong Zhao, Zhiwei Cheng, Kai Tian, Mengxiong Sun, Zhuoying Wang, Ming Jiao, Jens Luebeck, Kaiyuan Zhu, Xiao Zhang, Dongqing Zuo, Hongsheng Wang, Chongren Wang, Jiakang Shen, Xiaojun Ma, Gangyang Wang, Zongyi Wang, Jing Han, Kaiyuan Liu, Haoran Mu, Weiqi Ma, Yongyong Ren, Shibing Guo, Huangxin Tu, Lingfeng Yu, Yining Tao, Yu Lv, Hui Lu, Owen S. Chapman, Rishaan Kenkre, Lukas Chavez, Zhengdong Cai, Yuqin Yang, Wei Sun, Yafei Jiang, Yingqi Hua   +34 more
wiley   +1 more source

Understanding Small-Molecule Binding to MDM2: Insights into Structural Effects of Isoindolinone Inhibitors from NMR Spectroscopy

, 2011
The interaction between murine double minute (MDM2) and p53 is a major target in anticancer drug design. Several potent compound series, including the nutlins and spirooxindoles, have previously been established as high-affinity antagonists of MDM2.
Riedinger, Christiane, Hardcastle, Ian R., Ian R. Hardcastle, Wright, David J., Endicott, Jane A., James M. McDonnell, McDonnell, James M.; id_orcid, Noble, Martin E., Jane A. Endicott, Christiane Riedinger, Florian Mulks, Mulks, Florian, Martin E. Noble, David J. Wright   +13 more
core   +1 more source

CRISPR‐Scan: Cas13a Mismatch Tolerance Enabled Ultra‐Multiplexed Detection of Same‐Site Indels in Acute Myeloid Leukemia

Advanced Science, EarlyView.
Accurately detecting diverse same‐locus insertions or deletions (indels) remains challenging. This study reveals the mismatch‐tolerance profile of LwaCas13a and establishes CRISPR‐Scan, which uses a single crRNA to detect multiple same‐locus indels. The one‐pot assay detects nucleophosmin 1 (NPM1) mutant allele frequencies down to 0.01%, agrees with ...
Linlin Bai, Bei Wang, Mingmin Shi, Dianwei Liu, Huimin Ji, Ting Wang, Ziwei Wang, Kaiming Guo, Xinyang Dou, Chunyan Qian, Fang Zhang, Yongming Wang, Hongju Mao, Rui Wang   +13 more
wiley   +1 more source

Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes

Advanced Science, EarlyView.
Mitochondrial quality control (MQC) collapse redefines osteoarthritis, intervertebral disc degeneration, and osteoporosis as disorders of organelle dysfunction. Damaged mitochondria leak mtDNA and metabolites, driving cGAS‐STING inflammation, epigenetic reprogramming, and metabolic memory.
Haiyang Gao, Zhangrong Cheng, Xianglong Chen, Wenbo Wu, Wang Wu, Zimu Yu, Cao Yang, Yukun Zhang   +7 more
wiley   +1 more source