Results 61 to 70 of about 702,558 (291)

The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1

Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Phosphoinositide-dependent protein kinase-1 (PDK1) is an important protein in mediating the PI3K-AKT pathway and is thus identified as a promising target.
Xinyuan Xu, Yingyi Chen, Qiang Fu, Duan Ni, Jian Zhang, Xiaolong Li, Shaoyong Lu   +6 more
doaj   +1 more source

Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model [PDF]

Pharmacological Research, 2015
Cannabinoid pharmacology has proven nettlesome with issues of promiscuity a common theme among both agonists and antagonists. One recourse is to develop allosteric ligands to modulate cannabinoid receptor signaling. Cannabinoids have come late to the allosteric table.
Alex, Straiker, José, Mitjavila, Danielle, Yin, Anne, Gibson, Ken, Mackie   +4 more
openaire   +2 more sources

In vitro and in silico modelling of ROS1‐positive non‐small cell lung cancer reveals fusion‐dependent tyrosine kinase inhibitor responses

Molecular Oncology, EarlyView.
Drug resistance limits treatment success in a subset of lung cancers driven by ROS1 gene alterations. Using patient‐derived cells and computer simulations, we studied three key mutations and how they affect five targeted drugs. The mutations reduced drug effectiveness in different ways by altering protein structure and behavior.
Farhan Ul Haq, Marc Terrones, Felicia Rodrigues Fortes, Anne Schepers, Alessia Denis, Christophe Deben, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer   +8 more
wiley   +1 more source

Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor

Nature Communications
Positive allosteric modulators (PAMs) of the μ opioid receptor (MOR) offer a promising path toward safer opioid therapeutics, yet their mechanisms of action remain poorly understood.
Haonan Zhang, Kirill Konovalov, Alexandra K. Parpounas, Davide Provasi, Shifan Yang, Alejandro Abraham, Aileen M. Vela, Audrey L. Warren, Gregory Zilberg, Suri Wang, Marta Filizola, Daniel Wacker   +11 more
doaj   +1 more source

Positive allosteric adenosine A2A receptor modulation suppresses insomnia associated with mania- and schizophrenia-like behaviors in mice

Frontiers in Pharmacology, 2023
Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes.
Yang Lin, Koustav Roy, Shuji Ioka, Rintaro Otani, Mao Amezawa, Yukiko Ishikawa, Yoan Cherasse, Mahesh K. Kaushik, Daniela Klewe-Nebenius, Li Zhou, Masashi Yanagisawa, Yo Oishi, Yo Oishi, Tsuyoshi Saitoh, Tsuyoshi Saitoh, Michael Lazarus, Michael Lazarus   +16 more
doaj   +1 more source

Translating whole‐genome doubling into precision medicine in cancer

Molecular Oncology, EarlyView.
Whole‐genome doubling creates a WGD‐positive tumor state characterized by persistent chromosomal instability, karyotypic diversification, and cellular stress. These same biological pressures drive aggressive tumor evolution while exposing therapeutic vulnerabilities, providing a rationale for WGD‐informed precision medicine. Whole‐genome doubling (WGD)
Sejung Lee, Junghyeok Lim, Jinhyuk Bhin
wiley   +1 more source

Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

Acta Pharmaceutica Sinica B
Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful ...
Chunhao Zhu, Xiaobing Lan, Zhiqiang Wei, Jianqiang Yu, Jian Zhang   +4 more
doaj   +1 more source

Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response. [PDF]

PLoS Computational Biology, 2018
The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors.
Wei-Ven Tee, Enrico Guarnera, Igor N Berezovsky   +2 more
doaj   +1 more source

Allosteric Modulation of the CB1 Cannabinoid Receptor by Cannabidiol—A Molecular Modeling Study of the N-Terminal Domain and the Allosteric-Orthosteric Coupling

Molecules, 2021
The CB1 cannabinoid receptor (CB1R) contains one of the longest N termini among class A G protein-coupled receptors. Mutagenesis studies suggest that the allosteric binding site of cannabidiol (CBD) involves residues from the N terminal domain.
Jakub Jakowiecki, Renata Abel, Urszula Orzeł, Paweł Pasznik, Robert Preissner, Sławomir Filipek   +5 more
doaj   +1 more source

PASSer: Prediction of Allosteric Sites Server [PDF]

, 2020
Allostery is considered important in regulating protein\u27s activity. Drug development depends on the understanding of allosteric mechanisms, especially the identification of allosteric sites, which is prerequisite in drug discovery and design.
Xi, Jiang, Peng, Tao, Hao, Tian
core   +1 more source