Results 91 to 100 of about 121,181 (303)

Distinct potency of compounds targeting the T1R3 subunit in modulating the response of human sweet and umami taste receptors

Scientific Reports
The heterodimeric G-protein-coupled receptors T1R2/T1R3 and T1R1/T1R3 have been identified as sweet and umami taste receptors, respectively, and both of these receptors share the T1R3 subunit.
Maiko Kawasaki, Yuta Kidera, Ryusei Goda, Chiaki Taketani, Misato Ide, Wataru Fujii, Tomoya Nakagita, Takumi Misaka   +7 more
doaj   +1 more source

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

Pitfalls of NMDA Receptor Modulation by Neuroactive Steroids. The Effect of Positive and Negative Modulation of NMDA Receptors in an Animal Model of Schizophrenia

Biomolecules, 2021
Evidence from clinical and preclinical studies implicates dysfunction of N-methyl-D-aspartate receptors (NMDARs) in schizophrenia progression and symptoms.
Kristina Holubova, Marketa Chvojkova, Barbora Hrcka Krausova, Vojtech Vyklicky, Eva Kudova, Hana Chodounska, Ladislav Vyklicky, Karel Vales   +7 more
doaj   +1 more source

A Missense Mutation in the Seven-transmembrane Domain of the Human Ca2+ Receptor Converts a Negative Allosteric Modulator into a Positive Allosteric Modulator [PDF]

Journal of Biological Chemistry, 2006
G protein-coupled receptors (GPCRs) are the most common targets of drug action. Allosteric modulators bind to the seven-transmembrane domain of family 3 GPCRs and offer enhanced selectivity over orthosteric ligands that bind to the large extracellular N terminus.
Jianxin, Hu, Jiankang, Jiang, Stefano, Costanzi, Craig, Thomas, Wu, Yang, Jean H M, Feyen, Kenneth A, Jacobson, Allen M, Spiegel   +7 more
openaire   +2 more sources

Molecular dynamics simulations of positively selected codons in FcγRI reveal novel biochemical binding properties

FEBS Open Bio, EarlyView.
Evolutionary analysis across 32 placental mammals identified positive selection at residues H148 and W149 in the immune receptor FcγR1. Ancestral reconstruction combined with molecular dynamics simulations reveals how these mutations may influence receptor structure and dynamics, providing insight into the evolution of antibody recognition and immune ...
David A. Young, Omar Arias‐Gaguancela, Fiona Gibson, Morgan Grainger, Jodie Score, Amit Nathubhai, Mauricio Cafiero, Lee Richard Machado   +7 more
wiley   +1 more source

A Negative Allosteric Modulator for α5 Subunit-Containing GABA Receptors Exerts a Rapid and Persistent Antidepressant-Like Action without the Side Effects of the NMDA Receptor Antagonist Ketamine in Mice

eNeuro, 2017
New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility ...
P. Zanos, M. E. Nelson, Jaclyn N. Highland, Samuel R. Krimmel, Polymnia Georgiou, T. Gould, S. Thompson   +6 more
semanticscholar   +1 more source

Discovery of a Negative Allosteric Modulator of GABA_B Receptors

, 2016
Initialized from the scaffold of CGP7930, an allosteric agonist of GABAB receptors, a series of noncompetitive antagonists were discovered. Among these compounds, compounds 3, 6, and 14 decreased agonist GABA-induced maximal effect of IP3 production in ...
Zhi-Xiong Xia (1780636), Lin-Hai Chen (1780633), Yang Zhang (30734), Tong-Jie Xu (1780630), Jian-Feng Liu (260508), Bing Sun (44691), Fa-Jun Nan (62994)   +6 more
core   +1 more source

Mutant NPM1 in Acute Myeloid Leukemia Initiation and Maintenance

Aging and Cancer, EarlyView.
NPM1 mutations drive acute myeloid leukemia by acting as neomorphic transcriptional regulators that cooperate with Menin–MLL and XPO1 to sustain HOX/MEIS1 expression and block differentiation. Targeting these mutant‐specific transcriptional dependencies provides a rational therapeutic strategy for NPM1‐mutated AML.
Yanan Jiang, Zhong Fan, Runmeng Liu, Xiaotian Zhang   +3 more
wiley   +1 more source

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

Mutational Analysis and Modeling of Negative Allosteric Modulator Binding Sites in AMPA Receptors

Molecular Pharmacology, 2019
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) constitute a subclass of the ionotropic glutamate receptor superfamily, which functions as glutamate-gated cation channels to mediate the majority of excitatory neurotransmission
Charlotte Stenum-Berg, Maria Musgaard, Sergei Chavez-Abiega, C. L. Thisted, Lorenzo Barrella, P. C. Biggin, A. Kristensen   +6 more
semanticscholar   +1 more source