Results 71 to 80 of about 4,995,094 (293)

Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the mGluR2 Receptor [PDF]

ACS Medicinal Chemistry Letters, 2010
Novel oxazolobenzimidazoles are described as potent and selective positive allosteric modulators of the metabotropic glutamate receptor 2. The discovery of this class and optimization of its physical and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds (20 and 21) as advanced leads.
Robert M, Garbaccio, Edward J, Brnardic, Mark E, Fraley, George D, Hartman, Pete H, Hutson, Julie A, O'Brien, Brian C, Magliaro, Jason M, Uslaner, Sarah L, Huszar, Kerry L, Fillgrove, James H, Small, Cuyue, Tang, Yuhsin, Kuo, Marlene A, Jacobson   +13 more
openaire   +2 more sources

NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NAD+ biosynthesis

Molecular Oncology, EarlyView.
Loss of NAPRT promotes lung tumor initiation and growth through a noncanonical mechanism, independent of its role in NAD+ biosynthesis. Mechanistically, NAPRT depletion activates the mTORC2‐driven AKT/β‐catenin signaling axis to enhance clonogenic and invasive phenotypes. Furthermore, lung‐specific Naprt deletion significantly increases tumor burden in
Myung Joon Oh, Ji Yun Jang, Yoon Jeon, Gi‐Cheon Kim, Hwanho Lee, Jooyoung Lee, Ju‐Hwa Kim, Hakhyun Kim, Minjee Kim, Ho‐Keun Kwon, Ho Lee, Hyun Seok Kim   +11 more
wiley   +1 more source

Paclitaxel induces NM2‐dependent cellular contraction through GEF‐H1 dissociation from microtubules and RhoA/ROCK activation in cancer cells

Molecular Oncology, EarlyView.
Taxanes are widely used chemotherapeutics whose effects on cellular mechanics remain poorly understood. We show that paclitaxel induces rapid cellular contraction by promoting GEF‐H1 dissociation from microtubules and non‐muscle myosin II activation through RhoA/ROCK.
Gloria Asensio‐Juárez, Rafael Pérez‐Díaz, Hugo Ramos‐Solano, Marina Garrido‐Casado, Vanessa C. Talayero, Miguel Vicente‐Manzanares   +5 more
wiley   +1 more source

In Vivo Non-radioactive Assessment of mGlu5 Receptor-Activated Polyphosphoinositide Hydrolysis in Response to Systemic Administration of a Positive Allosteric Modulator

Frontiers in Pharmacology, 2018
mGlu5 receptor-mediated polyphosphoinositide (PI) hydrolysis is classically measured by determining the amount of radioactivity incorporated in inositolmonophosphate (InsP) after labeling of membrane phospholipids with radioactive inositol. Although this
Anna R. Zuena, Luisa Iacovelli, Rosamaria Orlando, Luisa Di Menna, Paola Casolini, Giovanni Sebastiano Alemà, Gabriele Di Cicco, Giuseppe Battaglia, Ferdinando Nicoletti, Ferdinando Nicoletti   +9 more
doaj   +1 more source

Heterotropic regulation and negative homotropic cooperativity

FEBS Open Bio, EarlyView.
We identified a structural module common to some proteins that couple negative cooperativity with heterotropic regulation, two features that rarely coexist. These proteins are ring‐like and present an ordered asymmetry whereby noncontacting subunits are symmetric, and their tertiary structure differs from that of contacting subunits.
Veronica Morea, Francesco Angelucci, Federica Arnesano, Gianmarco Pascarella, Patrizio Di Micco, Andrea Bellelli   +5 more
wiley   +1 more source

Allosteric modulators of metabotropic glutamate receptors: from virtual screening to experimental validation [PDF]

, 2007
The goal of this thesis was to gain further insight into the binding behavior of ligands in the heptahelical domain (HD) of group I metabotropic glutamate receptors (mGluRs).
Noeske, Tobias
core  

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator [PDF]

, 2020
Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing.
Gee, SM, Hoffmann, E, Nguyen, DP, Modgil, A, Hammond, RS, Davies, PA, Althaus, AL, Ackley, MA, Robichaud, AJ, Doherty, JJ, Salituro, FG, Belfort, GM, Quirk, MC, Moss, SJ, Dai, J, Kazdoba, TM   +15 more
core   +1 more source

Genetic dissection of human ABCE1 in yeast reveals separable requirements for ribosome recycling and suppression of aberrant reinitiation

FEBS Open Bio, EarlyView.
Human ABCE1 cannot functionally replace its yeast ortholog. Yeast–human chimera analysis identified NBD1 as a major interspecies barrier. Genetic screening yielded hABCE1 revertants that rescue yeast viability but fail to suppress aberrant translation reinitiation in the 3′ UTR.
Eriko Nakata, Yuxin Li, Kei Endo, Koichi Ito   +3 more
wiley   +1 more source

Positive allosteric modulation of a GPCR ternary complex

Science Advances
Abstract The activation of a G protein-coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterised by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and ...
Wessel A. C. Burger, Christopher J. Draper-Joyce, Celine Valant, Arthur Christopoulos, David M. Thal   +4 more
openaire   +2 more sources

Conformational Switching of Proteins on Material Surfaces Enabled by Peptide‐Oriented Adsorption

Advanced Functional Materials, EarlyView.
Responsive biointerfaces could be achieved using conformationally responsive proteins; however, their interconversion can be lost upon surface adsorption. Herein, we demonstrate that the incorporation a Au binding peptide into calmodulin allows for binding control on Au wherein the protein retains conformational switching. This capability was confirmed
Sakthirupini Ramamurthy, Kyle B. Meerbott, Lorenzo Travaglini, Garima S. Dobhal, Artur Sawicki, Marc R. Knecht, Tiffany R. Walsh, Dominic J. Glover   +7 more
wiley   +1 more source