Results 61 to 70 of about 19,105 (226)

Harnessing MDM2‐Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma

Advanced Science, EarlyView.
MDM2 dependency in pediatric sarcomas is driven by a novel p53‐independent oncogenic cistrome alongside canonical p53 pathway suppression. This study introduces MDM2‐recruiting transcriptional and epigenetic machinery degraders (MDM2‐TEMADs) as a novel precision oncology modality.
Jiawei Zhou, Xian Guan, Nan Li, Ying Zhang, Long Xie, Xingze Huang, Zhipeng Zhu, Zhuolin Ren, Xiaoyan Yu, Hanjun Guo, Yuanfang Wu, Lin Ma, Suya Zheng, Jingyao Zhang, Jiyang Liu, Victor Kuanmin Lee, Wenhao Chen, H. Phillip Koeffler, Jinhu Wang, Xin Han, Ye Chen, Liang Xu   +21 more
wiley   +1 more source

Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites

, 2019
Brd4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders.
Ziyang, Xu, Stefan, Kathman, Michael, Olp, Alexandar, Statsyuk, Daniel, Sprague, Brian, Smith   +5 more
core   +1 more source

Revisiting Target‐Aware de novo Molecular Generation with TarPass: Between Rational Design and Texas Sharpshooter

Advanced Science, EarlyView.
TarPass provides a rigorous benchmark for target‐aware de novo molecular generation by jointly evaluating protein‐ligand interactions, molecular plausibility, and drug‐likeness on 18 well‐studied targets. Results show that current models often fail to consistently surpass random baseline in target‐specific enrichment, while post hoc multi‐tier virtual ...
Rui Qin, Zijie Chen, Yurong Li, Meijing Fang, Longji Shen, Yilong Su, Odin Zhang, Qinghan Wang, Qun Su, Jike Wang, Tingjun Hou, Yu Kang   +11 more
wiley   +1 more source

Selective Antagonists of the Bronchiolar Epithelial NF-κB-Bromodomain-Containing Protein 4 Pathway in Viral-Induced Airway Inflammation

Cell Reports, 2018
Summary: The mechanisms by which the mammalian airway detects invading viral pathogens to trigger protective innate neutrophilic inflammation are incompletely understood.
Bing Tian, Zhiqing Liu, Jun Yang, Hong Sun, Yingxin Zhao, Maki Wakamiya, Haiying Chen, Erik Rytting, Jia Zhou, Allan R. Brasier   +9 more
doaj   +1 more source

Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Molecules, 2021
Bromodomain and extra-terminal domain (BET) subfamily is the most studied subfamily of bromodomain-containing proteins (BCPs) family which can modulate acetylation signal transduction and produce diverse physiological functions.
Siao Chen, Yi He, Yajiao Geng, Zhi Wang, Lu Han, Weiwei Han   +5 more
doaj   +1 more source

Stem Cell Differentiation Disperses Transcriptional Clusters via a Conserved Surface‐Condensate Trajectory

Advanced Science, EarlyView.
Stem cell differentiation follows a conserved surface condensate trajectory: H3K27ac super enhancers nucleate large RNA polymerase II clusters that grow and unfold before transcriptional activity disperses them. This work reveals how biophysical forces at enhancer surfaces dynamically build and dismantle stem cell transcription hubs, reshaping cell ...
Tim Klingberg, Irina Wachter, Agnieszka Pancholi, Matthias Akyel, Yomna Gohar, Priya Kumar, Ana Miguel Fernandes, Yuzhi Bao, Alica Schmidt‐Heydt, Marcel Piepers, Alicia Günthel, Marcel Sobucki, Elisa Kämmer, Süheyla Eroğlu‐Kayıkçı, Stephan Allgeier, Sylvia Erhardt, Vasily Zaburdaev, Carmelo Ferrai, Lennart Hilbert   +18 more
wiley   +1 more source

Brd4 471-730 functions as a DNI of the MCV LT and Brd4 interaction.

, 2012
A. Brd4 471-730 inhibits MCV LT and Brd4 Co-IP. 293T cells were co-transfected with pcDNA4C-MCV LT together with a pCDNA4C plasmid encoding Xpress-tagged Brd4 471-730 or the empty vector.
Jianxin You (121729), Christopher B. Buck (121726), Jing Li (10611), Rachel M. Schowalter (121719), Xin Wang (91924), Jing Jiao (121723)   +5 more
core   +1 more source

Brd4 modulates diet-induced obesity via PPARγ-dependent Gdf3 expression in adipose tissue macrophages

JCI Insight, 2021
Macrophage-mediated inflammatory response has been implicated in the pathogenesis of obesity and insulin resistance. Brd4 has emerged as a key regulator in the innate immune response.
Xiangming Hu, Xingchen Dong, Guo Li, Yanheng Chen, Jinjing Chen, Xiaoxin He, Hao Sun, Dong-Hyun Kim, Jongsook Kim Kemper, Lin-Feng Chen   +9 more
doaj   +1 more source

Membrane Fusion‐Mediated Cytosolic Delivery of Threose Nucleic Acids via Homotypic Nanoparticles Overcomes Drug Resistance in Triple‐Negative Breast Cancer

Advanced Science, EarlyView.
This study introduces a biomimetic “nanofusion” platform that integrates the biostability of threose nucleic acids (TNA) with homotypic cell‐membrane cloaking to combat drug‐resistant TNBC. By leveraging a non‐canonical membrane‐fusion pathway for direct cytosolic delivery, the platform bypasses endosomal sequestration. To achieve potent AKT2 silencing
Wei Zheng, Tristan Juin Han Chang, Xinchao Li, Zhongqi Zhou, Chung Tin, Kenward Vong, Pierre Karam, Pik Kwan Lo   +7 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