Discovery of potent allosteric antibodies inhibiting EGFR by Léxane Fournier, Lukas Pekar, Birgitta Leuthner, Harald Kolmar, Lars Toleikis, Stefan Becker

“…Our results suggest that allosteric antibodies may be potential new modalities for therapeutics.…”
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Insights into the Allosteric Regulation of Human Hsp90 Revealed by NMR Spectroscopy by Tjaša Goričan, Simona Golič Grdadolnik

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Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators by Lulu Yao, Qiang Zhou

“…In this review, we will focus on enhancing NMDAR functions, especially on the recent progress in the generation of subunit-selective, allosteric positive modulators (PAMs) of NMDARs. We shall also discuss the usefulness of these newly developed NMDAR-PAMs.…”
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Conformational diversity in class C GPCR positive allosteric modulation by Giuseppe Cannone, Ludovic Berto, Fanny Malhaire, Gavin Ferguson, Aurelien Fouillen, Stéphanie Balor, Joan Font-Ingles, Amadeu Llebaria, Cyril Goudet, Abhay Kotecha, Vinothkumar K.R., Guillaume Lebon

“…The mGlu receptors signal transduction can be allosterically potentiated by positive allosteric modulators (PAMs) binding to the 7TMs, which are of therapeutic interest in various neurological disorders. …”
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Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents by Frank Mazza, Alexandre Guet-McCreight, Thomas D. Prevot, Taufik Valiante, Etienne Sibille, Etay Hay

“…Background: Reduced cortical inhibition mediated by GABA (gamma-aminobutyric acid) is reported in depression, anxiety disorders, and aging. A novel positive allosteric modulator that specifically targets the α5-GABAA receptor subunit (α5-PAM), ligand GL-II-73 shows anxiolytic, antidepressant, and procognitive effects without the common side effects associated with nonspecific modulation by benzodiazepines such as diazepam, thus suggesting novel therapeutic potential. …”
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Targeting cryptic allosteric sites of G protein-coupled receptors as a novel strategy for biased drug discovery by Xin Qiao, Xiaolong Li, Mingyang Zhang, Ning Liu, Yanmei Wu, Shaoyong Lu, Ting Chen

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Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways by Renee Hastings, Arjun K. Aditham, Nicole DelRosso, Peter H. Suzuki, Polly M. Fordyce

“…By applying thermodynamic and kinetic models to these results and previous observations for the highly similar yet far more selective TF Pho4 (S. cerevisiae), we find that these mutations enhance selectivity by altering partitioning between or affinity within conformations with different intrinsic selectivity, providing a mechanistic basis for allosteric modulation of ligand selectivity. These results highlight the importance of conformational heterogeneity in determining sequence selectivity and can guide future efforts to engineer selective proteins.…”
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The efficacy of an allosteric modulator of the alpha 7 nicotinic acetylcholine receptor in a murine model of stroke by Katherine Hernandez, Nathan Jones, Sterling B. Ortega

“…Using a murine transient middle cerebral artery occlusion (tMCAO) model, we sought to evaluate the neurotherapeutic efficacy of a positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor (α7-nAChR), PNU-120596 (PNU), specifically examining whether PNU would modulate stroke-induced neurological dysfunction and neuropathology, with modulation of neuroinflammation as a possible mechanism.MethodsYoung male C57BL/6J mice received a subcutaneous injection of 20mg/kg of vehicle (DMSO) or PNU-120596 immediately after reperfusion, and infarct area and Bederson score were analyzed 24 hours post-stroke. …”
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Fragment Screening Identifies Novel Allosteric Binders and Binding Sites in the VHR (DUSP3) Phosphatase by Jiaqian Wu, Marek R. Baranowski, Alexander E. Aleshin, Eta A. Isiorho, Lester J. Lambert, Laurent J. S. De Backer, Ye Na Han, Ranajit Das, Douglas J. Sheffler, Andrey A. Bobkov, Alexis M. Lemberikman, Daniel A. Keedy, Nicholas D. P. Cosford, Lutz Tautz

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Formulation and characterization of CMPI nanoparticles for enhanced targeting of brain nicotinic receptors by positive allosteric modulator by Rahma Aly, Shoukath Sulthana, Robert Beaudoin, Ayman K. Hamouda, Santosh Aryal

“…Abstract 3-(2-Chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1 H-pyrazol-4-yl)isoxazole (CMPI) is a nicotinic acetylcholine receptor (nAChRs), one of the most subtype-selective a positive allosteric modulator (PAM) of nicotinic acetylcholine receptors (nAChRs). …”
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Correction: LRRK2 dynamics analysis identifies allosteric control of the crosstalk between its catalytic domains. by Jui-Hung Weng, Phillip C Aoto, Robin Lorenz, Jian Wu, Sven H Schmidt, Jascha T Manschwetus, Pallavi Kaila-Sharma, Steve Silletti, Constanza Torres-Paris, Sebastian Mathea, Deep Chatterjee, Stefan Knapp, Friedrich W Herberg, Susan S Taylor

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Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy by Amaury Herbet, Marie Hautière, Frédéric Jean-Alphonse, Delphine Vivier, Christophe Leboeuf, Narciso Costa, Aloïse Mabondzo, Guilhem Bousquet, Franck Denat, Eric Reiter, Didier Boquet

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A3 Adenosine Receptor Allosteric Modulator Induces an Anti-Inflammatory Effect: In Vivo Studies and Molecular Mechanism of Action by Shira Cohen, Faina Barer, Sara Bar-Yehuda, Adriaan P. IJzerman, Kenneth A. Jacobson, Pnina Fishman

“…The advantage of allosteric modulators is their capability to target specifically areas where adenosine levels are increased such as inflammatory and tumor sites, whereas normal body cells and tissues are refractory to the allosteric modulators due to low adenosine levels. …”
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Allosteric Fluorescent Detection of Saccharides and Biomolecules in Water from a Boronic Acid Functionalized Arene Ruthenium Assembly Hosting Fluorescent Dyes by Alaa Maatouk, Thibaud Rossel, Bruno Therrien

“…The intensity of the regained fluorescence is directly linked to the nature of the analyte, and it shows some dose–response relationships with saccharides and phosphorylated molecules that are not compatible with a displacement assay, thus suggesting an allosteric mechanism. Interestingly, when fluorescein is trapped by the metalla-rectangle in the presence of D-fructose, half of the maximum fluorescence intensity is recovered at a fructose concentration of 17.2 ± 4.7 μM, while, for D-glucose, a concentration of 50.6 ± 2.5 μM is required for the same effect. …”
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Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia by David Olivares-Berjaga, Albert Martínez-Pinteño, Natalia Rodríguez, Sergi Mas, Constanza Morén, Eduard Parellada, Patricia Gassó

“…One of these new therapies involves the positive allosteric modulators (PAMs) of metabotropic glutamate receptors, mainly types 2/3 (mGluR2/3). mGluR2/3 PAMs are selective for the receptor, present high tolerability and can modulate the activity of the receptor for long periods. …”
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Identifying Allosteric Small-Molecule Binding Sites of Inactive NS2B-NS3 Proteases of Pathogenic <i>Flaviviridae</i> by Hovakim Grabski, Siranuysh Grabska, Ruben Abagyan

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Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease?... by Antonio Daniele, Francesco Panza, Antonio Greco, Giancarlo Logroscino, Davide Seripa

“…Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only for GABAA receptors containing the α-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation of GABAA receptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. …”
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Allosteric coupling between G‐protein binding and extracellular ligand binding sites in GPR52 revealed by 19F‐NMR and cryo‐electron microscopy by Yanliu Fan, Xi Lin, Benxun Pan, Bo Chen, Dongsheng Liu, Kurt Wüthrich, Fei Xu

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Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes by Dasiel O. Borroto-Escuela, Karolina Wydra, Julia Pintsuk, Manuel Narvaez, Fidel Corrales, Magdalena Zaniewska, Luigi F. Agnati, Rafael Franco, Sergio Tanganelli, Luca Ferraro, Malgorzata Filip, Kjell Fuxe

“…Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. …”
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Τhiazolidine-4-One Derivatives with Variable Modes of Inhibitory Action Against DPP4, a Drug Target with Multiple Activities and Established Role in Diabetes Mellitus Type II by Dionysia Amanatidou, Phaedra Eleftheriou, Anthi Petrou, Athina Geronikaki, Theodoros Lialiaris

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