Results 111 to 120 of about 7,362 (230)

The Peptide PROTAC Modality: A New Strategy for Drug Discovery

MedComm
In recent years, proteolysis targeting chimera (PROTAC) technology has made significant progress in the field of drug development. Traditional drugs mainly focus on inhibiting or activating specific proteins, while PROTAC technology provides new ideas ...
Youmin Zhu, Yu Dai, Yuncai Tian
doaj   +1 more source

The c‐Src inhibitor eCF506 diminishes opioid tolerance and reduces β‐arrestin2 recruitment

British Journal of Pharmacology, EarlyView.
Morphine activation of μ receptors causes tolerance through c‐Src activation and β‐arrestin2 recruitment. c‐Src inhibition or degradation reduces β‐arrestin2 recruitment, μ receptor endocytosis, while causing receptor upregulation, all likely contributing to reduced morphine tolerance.
Samuel Singleton, Fraser Nunn, Erika Lace, Álvaro Lorente‐Macías, Rachel Toth, Asier Unciti‐Broceta, Tim G. Hales   +6 more
wiley   +1 more source

Daraxonrasib and Beyond: Pan‐RAS Inhibition, Resistance, and Next‐Generation Strategies

Cancer Science, EarlyView.
ABSTRACT RAS proteins have long been considered difficult therapeutic targets, but allele‐selective inhibitors established the clinical tractability of mutant RAS. Daraxonrasib (RMC‐6236), an oral pan‐RAS inhibitor, has now extended this concept by targeting multiple mutant and wild‐type RAS proteins.
Ryo Honda
wiley   +1 more source

Linker-free PROTACs efficiently induce the degradation of oncoproteins

Nature Communications
Proteolysis-targeting chimeras (PROTACs) present a potentially effective strategy against various diseases via selective proteolysis. How to increase the efficacy of PROTACs remains challenging.
Jianchao Zhang, Congli Chen, Xiao Chen, Kefan Liao, Fengming Li, Xiaoxiao Song, Chaowei Liu, Ming-Yuan Su, Huiyong Sun, Tingjun Hou, Chris Soon Heng Tan, Lijing Fang, Hai Rao   +12 more
doaj   +1 more source

TRIM59 Drives Bladder Cancer Progression Through E3 Ligase‐Dependent K48‐Linked Degradation of PTRF

Cancer Science, EarlyView.
Schematic model of TRIM59‐driven BLCA progression through K48‐linked ubiquitination and proteasomal degradation of PTRF, leading to AKT activation and c‐Myc upregulation. ABSTRACT Tripartite motif‐containing 59 (TRIM59) is an E3 ubiquitin ligase implicated in multiple malignancies, but its role in bladder cancer (BLCA) remains incompletely understood ...
Junlin Gan, Xuesong Bai, Aijie Zhang, Fei Lin, Hang Tong, Tinghao Li, Ning Xu, Xinyuan Li, Zhou Yu, Hubin Yin   +9 more
wiley   +1 more source

Targeting PCSK9 in Vascular Smooth Muscle Cells: An Effective Strategy to Suppress Ferroptosis and Attenuate Abdominal Aortic Aneurysm Progression

Cell Proliferation, EarlyView.
PCSK9 aggravates AAA by promoting ferroptosis in VSMCs. In the pathological AAA environment, PCSK9 upregulation triggers ferritinophagy‐dependent degradation of FTH1, leading to Fe2+ release, triggering lipid peroxidation and ferroptosis, exacerbating AAA.
Mengdie Xia, Man Li, Yanyu Chen, Jialin Chen, Yuting Cui, Xi‐Long Zheng, Jing Yang, Bingzhao Li, Xiaofeng Ma, Miao Liu, Gang Fan, Juan Peng, Xiaoyan Dai, Zhihan Tang   +13 more
wiley   +1 more source

Chromatin Remodeller BRD9 Orchestrates Odontoblastic Differentiation via Coordinating RUNX2‐KLF4

Cell Proliferation, EarlyView.
During odontoblast lineage commitment, the chromatin remodeller BRD9 acts as a critical epigenetic coordinator, orchestrating the chromatin landscape to facilitate synergistic binding of key transcription factors RUNX2 and KLF4 to target loci for odontogenesis.
Wenrui Zeng, Yuxiu Lin, Yongyan Gao, Delan Huang, Yuanyuan Li, Honglei Ruan, Guohua Yuan, Huan Liu, Zhi Chen   +8 more
wiley   +1 more source

A guide to transcriptional cyclin‐dependent kinases in cancer

The FEBS Journal, EarlyView.
Transcriptional cyclin‐dependent‐kinases (tCDKs) facilitate gene expression by promoting RNA polymerase II (RNAPII) progression through discrete phases of the transcription cycle. Aberrant tCDK activity is detectable in different human cancers, thereby contributing to de‐regulated gene expression programs that drive oncogenic phenotypes.
Jennifer R. Devlin, Salla Kyheröinen, Ricky W. Johnstone   +2 more
wiley   +1 more source

Histone deacetylase inhibitors as venetoclax‐sensitising partners in acute myeloid leukaemia: Mechanisms, pharmacology and translational perspectives

British Journal of Pharmacology, Volume 183, Issue 21, Page 6261-6290, November 2026.
Abstract Venetoclax combined with hypomethylating agents has improved treatment for older or unfit patients with acute myeloid leukaemia (AML), but resistance and relapse remain common. This review analyses the rationale for combining venetoclax with inhibitors of histone deacetylase (HDAC).
Jaebok Lee, Marc Diederich
wiley   +1 more source

Limiting Trial‐and‐Error: Linker‐Based 2D Descriptor Analysis to Support Very Early Proteolysis‐Targeting Chimeras Design

ChemMedChem, Volume 21, Issue 19, 14 October 2026.
Can simple linker descriptors guide PROTAC design? Analysis of matched CRBN‐ and VHL‐recruiting degraders shows that basic 2D linker properties may capture trends linked to degradation efficiency, in vitro ADME and physicochemical properties. A practical approach to reduce trial‐and‐error in early targeted protein degradation programs. Targeted protein
Giulia Apprato, Serena Traversa, Giulia Caron, Giuseppe Ermondi   +3 more
wiley   +1 more source