Results 101 to 110 of about 131,252 (300)

Systematic Position Mapping of Split CRISPR‐Cas12a Activators Enables Highly Sensitive miRNA Detection and Cancer Cell Stratification

Advanced Science, EarlyView.
ABSTRACT Amplification‐free Cas12a diagnostics with split crRNA enable rapid and programmable target recognition, yet insufficient understanding of DNA activator architecture prevents predictable control over trans‐cleavage activity and sensitivity. Here we systematically map over 200 split DNA activator configurations by introducing nicks at every ...
Xiaoyan Tang, Zhe Li, Yuning Lu, Miao Ma, Zijian Mo, Jiajun Ke, Xinyu Luan, Tiangang Luan, Junqiu Zhai   +8 more
wiley   +1 more source

Allosteric modulators for the A1-adenosine receptor

, 2004
A review. Allosteric modulators of endogenous adenosine represent an alternative to direct acting adenosine agonists and nucleoside uptake blockers. These compds. can selectively enhance the response to adenosine in only those organs or localized areas
ROMAGNOLI, Romeo, MOORMAN ALLAN R., BARALDI, Pier Giovanni, AGHAZADEH TABRIZI, Mojgan, PAVANI, Maria Giovanna   +4 more
core   +1 more source

Cancer‐Associated BCL‐2 Mutants Reveal Mechanisms Towards Venetoclax Resistance

Advanced Science, EarlyView.
Venetoclax (VEN) resistance in chronic lymphocytic leukemia arises from diverse BCL2 mutations. We map mechanisms contributing to VEN resistance across common BCL‐2 variants. G101V and D103Y reduce drug binding and increase sequestration of pro‐apoptotic proteins. V156D blocks VEN allosterically.
Jonas Aufdermauer, Ian de Ridder, Mahjoobeh Ehsani, Marasim Khan, Justin Kale, Lukas P. Frenzel, David Andrews, Spyridoula Karamanou, Ana J. Garcia‐Saez, Geert Bultynck   +9 more
wiley   +1 more source

Concentration dependence of the interaction of two allosteric modulators that compete for the same allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence of two allosteric modulators A and B competing for the same allosteric site, where α is either less than one (left) or greater than one (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

Pyrazole‐Derived Antibacterial Compounds Effectively Treat Methicillin‐Resistant Staphylococcus Aureus Infections by Inhibiting Aspartate Transcarbamoylase

Advanced Science, EarlyView.
This study unveils a novel antibacterial mechanism against MRSA, in which the compound Py‐27 selectively targets and inhibits aspartate transcarbamoylase (ATCase), a key enzyme in pyrimidine synthesis. This inhibition disrupts DNA replication, induces oxidative damage, leading to potent bactericidal activity.
Xiaorong Yang, Xinyuan Cao, Lixia Dai, Feng Yang, Jing Wang, Yudong Ma, Tong Bu, Zile Gong, Xueyan Liu, Changcai Bai, Xiaolou Miao, Xiaofei Shang   +11 more
wiley   +1 more source

Indomethacin Enhances Type 1 Cannabinoid Receptor Signaling

Frontiers in Molecular Neuroscience, 2019
In addition to its known actions as a non-selective cyclooxygenase (COX) 1 and 2 inhibitor, we hypothesized that indomethacin can act as an allosteric modulator of the type 1 cannabinoid receptor (CB1R) because of its shared structural features with the ...
Robert B. Laprairie, Robert B. Laprairie, Kawthar A. Mohamed, Ayat Zagzoog, Melanie E. M. Kelly, Melanie E. M. Kelly, Lesley A. Stevenson, Roger Pertwee, Eileen M. Denovan-Wright, Ganesh A. Thakur   +9 more
doaj   +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

Targeting cryptic allosteric sites of G protein-coupled receptors as a novel strategy for biased drug discovery

Pharmacological Research
G protein-coupled receptors (GPCRs) represent the largest family of membrane receptors and are highly effective targets for therapeutic drugs. GPCRs couple different downstream effectors, including G proteins (such as Gi/o, Gs, G12, and Gq) and β ...
Xin Qiao, Xiaolong Li, Mingyang Zhang, Ning Liu, Yanmei Wu, Shaoyong Lu, Ting Chen   +6 more
doaj   +1 more source

Allosteric modulators and selective agonists of muscarinic receptors

, 2006
Allosteric modulators of ligand-receptor interactions are found for a variety of receptors (Christopoulos, 2002). Allosteric agents attach to a binding site being topographically distinct from the site for conventional (orthosteric) agonists or ...
K. MOHR, U. HOLZGRABE, M. DE AMICI
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