Results 91 to 100 of about 4,995,094 (293)

Computational Analysis of Negative and Positive Allosteric Modulator Binding and Function in Metabotropic Glutamate Receptor 5 (In)Activation

, 2016
Metabotropic glutamate receptors (mGluRs) are high-profile G-protein coupled receptors drug targets because of their involvement in several neurological disease states, and mGluR5 in particular is a subtype whose controlled allosteric modulation, both ...
Xavier Gómez-Santacana (2106892), Amadeu Llebaria (1626844), Jesús Giraldo (1558987), James A. R. Dalton (2106895)   +3 more
core   +1 more source

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

Pharmacological characterisation of S 47445, a novel positive allosteric modulator of AMPA receptors.

PLoS ONE, 2017
S 47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPA-PAM). S 47445 enhanced glutamate's action at AMPA receptors on human and rat receptors and was inactive at NMDA and ...
Sylvie Bretin, Caroline Louis, Laure Seguin, Stéphanie Wagner, Jean-Yves Thomas, Sylvie Challal, Nathalie Rogez, Karine Albinet, Fabrice Iop, Nadège Villain, Sonia Bertrand, Ali Krazem, Daniel Bérachochéa, Stéphanie Billiald, Charles Tordjman, Alex Cordi, Daniel Bertrand, Pierre Lestage, Laurence Danober   +18 more
doaj   +1 more source

MK-7622: A First-in-Class M₁ Positive Allosteric Modulator Development Candidate

, 2018
Identification of ligands that selectively activate the M1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders.
Kenneth A. Koeplinger (1811914), Charles D. Thompson (1811923), Christina N. Di Marco (2268625), Scott D. Kuduk (1811911), Matthew A. Seager (1811908), Joy Fuerst (5175641), George D. Hartman (2183106), Lei Ma (221178), William J. Ray (190662), Ronald K. Chang (2013505), Thomas J. Greshock (2178438), Marion Wittmann (1811926), Mark T. Bilodeau (1779970), Douglas C. Beshore (2414380)   +13 more
core   +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

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

Direct activation of M1 muscarinic receptors by the positive allosteric modulator, BQCA

, 2014
BQCA (Benzyl quinolone carboxylic acid) was recently identified as a positive allosteric modulator of the M1 muscarinic receptor. We studied the nature of this effect on muscarinic signaling at the single cell level in Chinese Hamster Ovary (CHO) cells ...
Brinker, Katherine
core   +1 more source

T‐495, a novel low cooperative M1 receptor positive allosteric modulator, improves memory deficits associated with cholinergic dysfunction and is characterized by low gastrointestinal side effect risk

Pharmacology Research & Perspectives, 2020
M1 muscarinic acetylcholine receptor (M1R) activation can be a new therapeutic approach for the treatment of cognitive deficits associated with cholinergic hypofunction. However, M1R activation causes gastrointestinal (GI) side effects in animals.
Takao Mandai, Yuu Sako, Emi Kurimoto, Yuji Shimizu, Minoru Nakamura, Makoto Fushimi, Ryouta Maeda, Maki Miyamoto, Haruhide Kimura   +8 more
doaj   +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