Results 41 to 50 of about 37,458 (256)

Analysis of positive and negative allosteric modulation in metabotropic glutamate receptors 4 and 5 with a dual ligand

Scientific Reports, 2017
As class C GPCRs and regulators of synaptic activity, human metabotropic glutamate receptors (mGluRs) 4 and 5 are prime targets for allosteric modulation, with mGlu5 inhibition or mGlu4 stimulation potentially treating conditions like chronic pain and ...
James A. R. Dalton, Jean-Philippe Pin, Jesús Giraldo   +2 more
doaj   +1 more source

Mapping the Interface of a GPCR Dimer: A Structural Model of the A2A Adenosine and D2 Dopamine Receptor Heteromer

Frontiers in Pharmacology, 2018
The A2A adenosine (A2AR) and D2 dopamine (D2R) receptors form oligomers in the cell membrane and allosteric interactions across the A2AR–D2R heteromer represent a target for development of drugs against central nervous system disorders.
Dasiel O. Borroto-Escuela, David Rodriguez, Wilber Romero-Fernandez, Jon Kapla, Mariama Jaiteh, Anirudh Ranganathan, Tzvetana Lazarova, Kjell Fuxe, Jens Carlsson   +8 more
doaj   +1 more source

IMPDH inhibition enhances cytarabine efficacy in SAMHD1‐expressing leukaemia cells via guanine nucleotide depletion

Molecular Oncology, EarlyView.
Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors revealed that IMPDH inhibitors selectively sensitise SAMHD1‐proficient AML cells to cytarabine.
Miriam Yagüe‐Capilla, Christopher Dirks, Caroline Eiden, Sonja K. Fesenmayer, Femke M. Hormann, Yolande Klootsema, Ingrid Lilienthal, Si Min Zhang, Nikolas Herold, Sean G. Rudd   +9 more
wiley   +1 more source

Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids.

PLoS ONE, 2011
Glycine receptors (GlyRs) are transmitter-gated anion channels of the Cys-loop superfamily which mediate synaptic inhibition at spinal and selected supraspinal sites.
Gonzalo E Yévenes, Hanns Ulrich Zeilhofer   +1 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

Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer

Molecular Oncology, EarlyView.
Dysregulation of the Hippo pathway drives nuclear accumulation of YAP/TAZ, activating stemness‐related transcriptional programs that sustain breast cancer stemness and fuel therapeutic resistance across subtypes, underscoring Hippo signaling as a targetable vulnerability. Figure created and edited with BioRender.com.
Giulia Schiavoni, Antonella Palmese, Stefano Scalera, Laura Cipriani, Davide Mascolo, Patrizia Vici, Teresa Arcuri, Lorena Filomeno, Eriseld Krasniqi, Giovanni Blandino, Giulia Bon, Marcello Maugeri‐Saccà   +11 more
wiley   +1 more source

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

Allosteric modulation of G protein-coupled receptor signaling

Frontiers in Endocrinology, 2023
G protein-coupled receptors (GPCRs), the largest family of transmembrane proteins, regulate a wide array of physiological processes in response to extracellular signals. Although these receptors have proven to be the most successful class of drug targets,
Siyuan Shen, Chang Zhao, Chao Wu, Suyue Sun, Ziyan Li, Wei Yan, Zhenhua Shao   +6 more
doaj   +1 more source

Interpreting the effects of DNA polymerase variants at the structural level

Molecular Oncology, EarlyView.
Using MAVISp and molecular dynamics simulations, we analyzed over 60 000 missense variants in POLE and POLD1 from ClinVar, COSMIC, cBioPortal, and saturation mutagenesis. Identified mechanistic indicators, including stability, binding, and long‐range, enable structural interpretation, providing ACMG‐like evidence for possible reclassification of VUS ...
Matteo Arnaudi, Karolina Krzesińska, Ludovica Beltrame, Pablo Sánchez‐Izquierdo Besora, Matteo Tiberti, Mef Nilbert, Anna Rohlin, Elena Papaleo   +7 more
wiley   +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