Results 111 to 120 of about 8,155 (246)

Transcriptomic and metabolomic analyses reveal that lobeglitazone ameliorates hepatic steatosis in rats concurrent with regulation of mitochondrial pyruvate metabolism

British Journal of Pharmacology, EarlyView.
Background and Purpose Lobeglitazone is a thiazolidinedione and PPARγ agonist that improves metabolic parameters and hepatic steatosis, but its mechanisms are not fully understood. This study investigated the effects of lobeglitazone on hepatic transcriptomic and metabolic profiles in a rat model of obesity and Type 2 diabetes mellitus.
Hyekyung Yang, Su Young Son, Youngmi Song, Hyewon Choi, In‐Gu Do, Choong Hwan Lee, Cheol‐Young Park   +6 more
wiley   +1 more source

Inhibition of leucine‐rich kinase 2 (LRRK2) promotes peripheral axon regeneration via phosphorylation‐network remodelling

British Journal of Pharmacology, EarlyView.
Background and Purpose In contrast to neurons in the central nervous system, neurons in the peripheral nervous system can regenerate axons after injury via activation of a pro‐regenerative transcriptional programme. Pathogenic mutations in leucine‐rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, and several small ...
Eun‐Hae Jang, Eun Mo Yang, Gil Song, Seung Min Park, Harryn Choi, Jaeyong Kim, Chanil Kim, Yunho Gim, Hyuk‐Joo Jeon, Yewon Cho, Jong Bae Park, Eun‐Mi Hur   +11 more
wiley   +1 more source

sGC stimulator BAY 41‐8543 improves survival and ventricular function in a rat model of doxorubicin‐induced cardiomyopathy with nephrotic syndrome

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Anthracyclines such as doxorubicin (DOXO) remain a cornerstone of cancer therapy but are associated with a high risk of cardiotoxicity and subsequent heart failure (HF). Impairment of NO/soluble guanylyl cyclase (sGC)/cGMP pathway has been reported in anthracycline‐induced cardiomyopathy.
Olga Gawrys, Petra Škaroupková, Soňa Kikerlová, Zdeňka Vaňourková, Martina Hüttl, Olga Lenčová, Kasin Yadunandam Anandam, Svenja Stomberg, Sönke Behrends, Barbara Szeiffová Bačová, Matúš Sykora, Lisa Dietz, Peter Sandner, Luděk Červenka, Martin Štěrba   +14 more
wiley   +1 more source

Targeting peroxynitrite production in a model of persistent temporomandibular disorder comorbid with migraine

British Journal of Pharmacology, EarlyView.
Background and Purpose The persistence of temporomandibular disorders (TMDs), particularly myogenous, in a person with migraine can lead to exacerbated clinical outcomes and limited response to treatment. The pro‐nociceptive reactive nitroxidative species, peroxynitrite, is involved in migraine mechanisms, but little is known of its role in this ...
Simon Akerman, Ana Belen Salinas‐Abarca, Wei Guo, Daniela Salvemini, Marcela Romero‐Reyes   +4 more
wiley   +1 more source

Potentiation effects of the positive allosteric modulator PTC‐174 on NMDA receptors in neonatal male rat substantia nigra dopaminergic neurons

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Positive allosteric modulators bind to secondary binding sites on the receptor and alter receptor conformation and activation, changing agonist potency and efficacy. PTC‐174 is a novel NMDA receptor positive allosteric modulator that particularly enhances activity of receptors containing GluN2C or GluN2D subunits.
Bangyuan Liu, Alasdair J. Gibb
wiley   +1 more source

Receptor kinetics: Binding flux‐based approaches offer complementary insight into how ligand binding evolves with time

British Journal of Pharmacology, EarlyView.
Background and Purpose Binding kinetics are essentially based on rate constants. Yet, this view has been challenged by the idea that ‘binding fluxes’ are dynamic and therefore more relevant. Those fluxes refer to the rate at which a target/receptor changes from one state into another through ligand/drug binding or a conformational change.
Georges Vauquelin, Terry Kenakin, Dominique Maes   +2 more
wiley   +1 more source

MCL‐1 inhibition triggers a largely reversible cardiac stress signature in a humanised mouse model

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Myeloid cell leukaemia‐1 (MCL‐1) is an essential anti‐apoptotic protein and a promising therapeutic target in oncology. Early clinical studies of MCL‐1 inhibitors reported unexpected elevations in cardiac troponin, raising concerns about potential cardiotoxicity.
Markus B. Heckmann, Zsanett Papdi, Nils J. Strauch, Daniel Finke, Marc‐Steffen Raab, Antje Blank, Norbert Frey, Lorenz H. Lehmann   +7 more
wiley   +1 more source

Chemoproteomic discovery of a brain‐penetrant, covalent NLRP3 inhibitor that binds a novel allosteric pocket

British Journal of Pharmacology, EarlyView.
NLRP3 is a promising inflammatory target, but existing inhibitors lack diversity and brain penetrance, and none are approved. Using chemoproteomics, we discovered a novel series that binds to Cys463 in a previously uncharacterized pocket. Compounds showed nanomolar potency, brain exposure, and in vivo suppression of IL‐1β, supporting neuroinflammatory ...
Donald C. Rogness, Evelyn P. Sievert, Vincent F. Vartabedian, Steffen M. Bernard, Erick Aitchison, William Tao, Mikaela Lindvall, Jing Qian, Christie L. Eissler, Brian E. Nordin, Benjamin D. Horning, Cian Kingston, Kelsey N. Lamb, Joshua C. Bell, Bingwen Lu, Jonathan Pollock, Jun Shi, Roli Khattri, David S. Weinstein, Matthew P. Patricelli, Brian N. Cook, Gabriel M. Simon   +21 more
wiley   +1 more source

Selective modulation of NaV channel gating counteracts aberrant hyperexcitability and rescues motor function and survival in a model of spinal muscular atrophy

British Journal of Pharmacology, EarlyView.
Background and Purpose Spinal muscular atrophy (SMA) is a motor neuron disease caused by SMN1 gene loss, leading to reduced survival motor neuron (SMN) protein and progressive motor neuron degeneration. Although SMN‐restoring therapies improve outcomes, residual disease burden and non‐curative efficacy underscore the need for complementary treatments ...
Fernanda C. Cardoso, Jessica A. I. Muller, Yougang Zhang, Jean Giacomotto   +3 more
wiley   +1 more source

NMDA receptor subunit‐dependent analysis of radiprodil inhibition in neonatal male rat substantia nigra dopaminergic neurons

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Radiprodil is a GluN2B subunit selective NMDA receptor negative allosteric modulator which is currently under clinical investigation as a possible anti‐epileptic drug for paediatric use. Our goal was to investigate the inhibition of dopaminergic neuron NMDA responses by radiprodil.
Bangyuan Liu, Alasdair J. Gibb
wiley   +1 more source