Results 91 to 100 of about 137,279 (309)

Deconstructing Allostery: Computational Assessment of the Binding Determinants of Allosteric PTP1B Modulators

, 2023
It is currently challenging to predict whether fragment hits that do not bind to an orthosteric site could be elaborated into allosteric modulators, as in these cases binding does not necessarily translate into a functional effect.
Silvia, Lovera, Adele, Hardie, Benjamin P, Cossins, Julien, Michel   +3 more
core   +1 more source

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

Advanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel, Sofia Kokkaliari, Qiwen Gao, Jinjing Chen, Larissa Costa de Almeida, Srinivasarao Tenneti, Derek A. Leas, Eli Levit, Lewis S. Alexander, Khalil A. Abboud, Pingrong Wei, Michael D. Cameron, James R. Rocca, Ranjala Ratnayake, Donna D. Zhang, Hendrik Luesch, Robert W. Huigens III   +16 more
wiley   +1 more source

Allosteric Inhibition of P-Glycoprotein-Mediated Efflux by DMH1

Biomedicines
Background/Objectives: P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, plays a key role in multidrug resistance by actively exporting chemotherapeutic agents and xenobiotics from cells.
Zhijun Wang, Chen Xie, Maggie Chou, Jijun Hao   +3 more
doaj   +1 more source

Small Molecule Targeting of Protein–Protein Interactions through Allosteric Modulation of Dynamics

Molecules, 2015
The protein–protein interaction (PPI) target class is particularly challenging, but offers potential for “first in class” therapies. Most known PPI small molecules are orthosteric inhibitors but many PPI sites may be fundamentally intractable to this ...
Benjamin P. Cossins, Alastair D. G. Lawson   +1 more
doaj   +1 more source

Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects.

, 2015
Activation of nicotinic acetylcholine receptors (nAChRs) is associated with the binding of agonists such as acetylcholine to an extracellular site that is located at the interface between two adjacent receptor subunits.
Dhankher, P, Gill-Thind, JK, D'Oyley, JM, Sheppard, TD, Millar, NS   +4 more
core  

Calculating Transfer Entropy from Variance-Covariance Matrices Provides Insight into Allosteric Communication in ERK2

, 2020
Transfer entropy methods provide an approach to understanding asymmetric information flow in coupled systems, with particular application to understanding allosteric interactions in biomolecular systems.
Daniel, Barr, Benjamin, Ahlbrecht, Luisa, Garcia Michel, Clara, Keirns   +3 more
core   +1 more source

Fibrates Inhibit PLTP‐induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs

Advanced Science, EarlyView.
Phospholipid transfer protein(PLTP) plays a critical role in forming a complex with kinase A (AURKA) and P65. This interaction facilitates phosphorylation of P65 at Ser536, leading to the activation of the NF‐κB signaling pathway. Ultimately, this leads to the upregulation of downstream cytokines, including IL‐6, IL‐8, and CSF‐1, which promotes M2 ...
Xinyue Liang, Yaning Li, Jianxun Cai, Lisi Luo, Pengfei Yang, Yutong Chen, Jiancong Zhou, Yan Zeng, Jiaping Yu, Weiyu Zhang, Wenzheng Pang, Yufang Li, Chunhua Wen, Jian Li, Linjuan Zeng   +14 more
wiley   +1 more source

Functional Analysis of Ligand‐Gated Chloride Channels in a Cnidarian Sheds Light on the Evolution of Inhibitory Signaling

Advanced Science, EarlyView.
We uncover a large variety of putative inhibitory ligand‐gated ion channels (LGICs) in the phylum Cnidaria, the sister group to all bilaterian animals. Phylogenetic analysis suggests a complex evolutionary history of inhibitory LGICs with diverse neurotransmitter ligands.
Abhilasha Ojha, Linda Kloss, Juan D. Montenegro, Simone Albani, Audrey Ortega‐Ramírez, Mihaela Raycheva, Sylvia Joussen, Sabrina Kaul, Michèle Bachmann, Lisa Huf, Günther Schmalzing, Alison G. Cole, Ulrich Technau, Stefan Gründer   +13 more
wiley   +1 more source

Recent Advances in the Discovery of CK2 Allosteric Inhibitors: From Traditional Screening to Structure-Based Design

Molecules, 2020
Protein kinase (CK2) has emerged as an attractive cancer therapeutic target and recent efforts have been made to develop its inhibitors. However, the development of selective inhibitors remains challenging because of the highly conserved ATP-binding ...
Xiaolan Chen, Chunqiong Li, Dada Wang, Yu Chen, Na Zhang   +4 more
doaj   +1 more source

Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor

, 2023
International audienceThe α7 nicotinic acetylcholine receptor (nAChR), a potential drug target for treating cognitive disorders, mediates communication between neuronal and non- neuronal cells. Although many competitive antagonists, agonists, and partial-
Stéphanie Pons, Prevost, Marie, S, de la Bâtie, Gabrielle, Dejean, Nathalie Barilone, Aymé, Gabriel, Baachaoui, Rayen, Corringer, Pierre-Jean, Ákos Nemecz, Marie S. Prevost, Pons, Stéphanie, Rayen Baachaoui, Barilone, Nathalie, Gabriel Aymé, Uwe Maskos, Pierre Lafaye, Lafaye, Pierre, Qimeng Li, Nemecz, Ákos, Li, Qimeng, Gabrielle Dejean de la Bâtie, Maskos, Uwe, Pierre-Jean Corringer   +21 more
core   +1 more source