Results 101 to 110 of about 3,750,504 (279)

Advances in the Structural Basis of GluN2A-Selective Negative Allosteric Modulators

ACS Medicinal Chemistry Letters
N-Methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels that play a critical role in synaptic plasticity, learning, and memory in the central nervous system (CNS). These receptors assemble into functionally diverse complexes composed of GluN1, GluN2, and GluN3 subunits.
Yinlong Li, Hongjie Yuan, Steven H. Liang   +2 more
openaire   +2 more sources

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

The Ascaris suum nicotinic receptor, ACR-16, as a drug target: Four novel negative allosteric modulators from virtual screening

International Journal for Parasitology: Drugs and Drug Resistance, 2016
Soil-transmitted helminth infections in humans and livestock cause significant debility, reduced productivity and economic losses globally. There are a limited number of effective anthelmintic drugs available for treating helminths infections, and their ...
Fudan Zheng, Alan P. Robertson, Melanie Abongwa, Edward W. Yu, Richard J. Martin   +4 more
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

Development of novel, cns penetrant mglu3 selective negative allosteric modulator probes derived from a closely related mglu5 positive allosteric modulator

, 2012
Metabotropic glutamate (mGlu) receptors are examples of family C G-protein-coupled receptors that possess vast roles in the pathophysiology of central nervous system (CNS) disorders.
Bruner, Joshua Andrew
core  

Concentration dependence of the interaction of two allosteric modulators binding each to its own allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence two allosteric modulators A and B each binding to its own site, where A is either positive (left) or negative (right) and B is negative allosteric modulator.
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

A thieno[2,3-d]pyrimidine scaffold is a novel negative allosteric modulator of the dopamine D2 receptor [PDF]

, 2018
Recently, a novel negative allosteric modulator (NAM) of the D 2-like dopamine receptors 1 was identified through virtual ligand screening. This ligand comprises a thieno[2,3-d]pyrimidine scaffold that does not feature in known dopaminergic ligands ...
Kellam, Barrie, Tim J. Fyfe, Fyfe, Tim J., Capuano, Ben, Peter J. Scammells, Ben Capuano, Zarzycka, Barbara, Herman D. Lim, J. Robert Lane, Katrich, Vsevolod, Scammells, Peter J., Lane, J. Robert, Vsevolod Katrich, Lim, Herman D., Barrie Kellam, Barbara Zarzycka, Shailesh N. Mistry, Mistry, Shailesh N.   +17 more
core   +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

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