Results 101 to 110 of about 692,160 (279)

Targeting Tex10 Overcomes Oxaliplatin Resistance by Competitively Disrupting the Non‐Canonical BAF Complex in Colorectal Cancer

Advanced Science, EarlyView.
This study reveals that Tex10 drives oxaliplatin resistance in colorectal cancer by competitively binding BRD9 to disrupt the ncBAF complex, thereby suppressing AMBRA1 transcription and ULK1‐mediated autophagy. Gemcitabine is identified as a direct Tex10 inhibitor that restores autophagy and overcomes resistance.
Ping Xu, Jie Huang, Xiaojin Gao, Lin Deng, Yanheng Deng, Denglu Wang, Chunlei Yu, Yunxiang Zhang, Jingdong Li, Xiaocong Xiang   +9 more
wiley   +1 more source

Exploring the Allosteric Pathways of Asciminib in the Dual Inhibition of BCR-ABL1

Biomolecules
The BCR-ABL1 fusion protein is a critical therapeutic target in Chronic Myeloid Leukemia (CML). Current monotherapy approaches involve types of inhibitors that can be categorized into ATP competitive inhibitors and allosteric inhibitors.
Jie Ming, Hongwei Gao, Jiuyu Zhan
doaj   +1 more source

Continuous Evolution System Based on Toxin–Antitoxin System Combined with Base Deaminase Accelerates the In Vivo Modification of Target Proteins

Advanced Science, EarlyView.
The promoted Escherichia coli‐assisted continuous evolution (PEACE) system operates through a stringent three step genetic circuit: target gene mutation via a deaminase–T7 RNA polymerase (T7 RNAP) fusion, coupling variant function to antitoxin expression, and growth based selection of surviving cells.
Xinyu Zhang, Zhanzhi Liu, Ying Xu, Mingjing Sun, Guangzhen Zhou, Deming Rao, Xiaoqian Chen, Sheng Wang, Zhigang Li, Yan Huang, Jing Wu   +10 more
wiley   +1 more source

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

Advanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu, Hongyuan Zhang, Tayyiba Azam, Susanne S. Hille, Yingjuan Liu, Min Zi, Jiaqing Lang, He Yu, Yujia Cao, Bernard D. Keavney, Tamer M. A. Mohamed, Jessica M. Miller, Riham R. E. Abouleisa, Ming Xu, Elizabeth J. Cartwright, Oliver J. Müller, Ming Lei, Xin Wang   +17 more
wiley   +1 more source

DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated‐Acute Kidney Injury

Advanced Science, EarlyView.
This study identifies a potential therapeutic approach for sepsis‐associated acute kidney injury (SA‐AKI). We found that during SA‐AKI, reduced expression of DDX3x in renal tubular epithelial cells mediates histone delactylation, which in turn upregulates NINJ1 transcription and triggers tubular cell death. Conversely, Odetiglucan confers protection by
Hongyu Liang, Jihong Jiang, Huanxin Yin, Chunyan Liu, Hongjun Huang, Yan Luo, Minmin Zhu, Qiuyun Wang   +7 more
wiley   +1 more source

Allosteric kinase inhibitors

, 2017
Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalytic site-directed tyrosine kinase inhibitor (TKI). Objectives. Pathophysiologic role of the BCR-ABL1
Hantschel, Oliver, Ottmann, Oliver G.
openaire   +1 more source

Transcription Factor HOXC11 Drives Colorectal Cancer Progression and Metastasis via CAMK2A‐Dependent CXCL5 Upregulation

Advanced Science, EarlyView.
HOXC11 drives colorectal cancer progression by transcriptionally activating CAMK2A, which triggers NF‐κB–dependent CXCL5 upregulation. CXCL5–CXCR2 signaling further reinforces HOXC11 expression through the ERK1/2–SP1 axis, forming a prometastatic positive feedback loop that is effectively disrupted by combined CAMK2A and CXCR2 inhibition.
Qingyang Sun, Hengjie Xu, Sheng Yang, Jiahui Zhou, Chuanxin Tian, Hongxu Nie, Chi Jin, Tuo Wang, Zhihao Chen, Junwei Tang, Yifei Feng, Xiaowei Wang, Yueming Sun   +12 more
wiley   +1 more source

Allosteric modulators of metabotropic glutamate receptors: from virtual screening to experimental validation [PDF]

, 2007
The goal of this thesis was to gain further insight into the binding behavior of ligands in the heptahelical domain (HD) of group I metabotropic glutamate receptors (mGluRs).
Noeske, Tobias
core  

Selective Modulation of OTUB1 Noncanonical Function via a bioPhosTAC Strategy

Advanced Science, EarlyView.
This work positions the versatile performance of the peptide‐based bioPhosTAC platform for dissecting phosphorylation‐dependent biology and expanding the scope of induced‐proximity technologies. We demonstrated that selective manipulation of a tyrosine phosphorylation site is sufficient to propagate coordinated cellular consequences.
Seung Un Seo, Seon Min Woo, Minhyeong Choi, Soeun Rhee, Simmyung Yook, Donghyuk Shin, Kwang‐Su Park, Taeg Kyu Kwon   +7 more
wiley   +1 more source

Allosteric Inhibitors Have Distinct Effects, but Also Common Modes of Action, in the HCV Polymerase [PDF]

, 2015
The RNA-dependent RNA polymerase from the Hepatitis C Virus (gene product NS5B) is a validated drug target because of its critical role in genome replication.
Davis, Brittny C., Brown, Jodian A., Thorpe, Ian F.   +2 more
core   +1 more source