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| http://dx.doi.org/10.18632/oncoscience.388 | DOI Listing |
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The basic income for care leavers in Wales pilot evaluation: Protocol of a quasi-experimental evaluation.
PLoS One
October 2024
Cardiff University, School of Social Sciences, Cardiff, United Kingdom.
Background: This study will evaluate the Basic Income for Care Leavers in Wales pilot (BIP), which is the most generous basic income scheme in the world. A cohort of care-experienced young people who become aged 18 during a 12-month enrolment period (July 2022-June 2023) are receiving £1,600 (before tax) per month for two years, and the Welsh Government intends this to have a range of benefits. This evaluation will examine the impact of BIP, the implementation of the pilot and how it is experienced, and its value for money.
View Article and Find Full Text PDFPackaging of alphavirus-based self-amplifying mRNA yields replication-competent virus through a mechanism of aberrant homologous RNA recombination.
mBio
October 2024
Wageningen University and Research, Laboratory of Virology, Wageningen, the Netherlands.
Messenger (m)RNA has taken center stage in vaccine development, gene therapy, and cancer immunotherapy. A next-generation of mRNA is the self-amplifying (sa)mRNA, which induces broad and long-lasting immunity at a lower dose which provides better clinical outcomes in conjunction with fewer adverse effects. SamRNA, also known as "replicon" RNA, encodes the replication machinery of an alphavirus together with an antigen.
View Article and Find Full Text PDFIsoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs.
Biochem Pharmacol
November 2024
Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia. Electronic address:
Class B1 G protein-coupled receptors (GPCRs) are peptide hormone receptors and well validated therapeutic targets, however development of non-peptide drugs targeting this class of receptors is challenging. Recently, a series of isoquinoline-based derivates were reported in the patent literature as allosteric ligands for the glucagon receptor subfamily, and two compounds, LSN3451217 and LSN3556672, were used to facilitate structural studies with the glucagon-like peptide-1 receptor (GLP-1R) and glucose dependent insulinotropic peptide receptor (GIPR) bound to orthosteric agonists. Here we pharmacologically characterized stereoisomers of LSN3451217 and LSN3556672, across the class B1 GPCR family.
View Article and Find Full Text PDFDiffusing protein binders to intrinsically disordered proteins.
bioRxiv
July 2024
Department of Biochemistry, University of Washington, Seattle, WA, USA.
Article Synopsis
- Proteins that can specifically bind to intrinsically disordered proteins (IDPs) and regions (IDRs) have great potential for therapy and diagnostics, but no general method exists for targeting them.
- This study introduces RFdiffusion, a technique that, starting from the target protein sequence, generates binders for various IDPs and IDRs in multiple conformations with affinities ranging from 3 to 100 nM.
- The generated binders, like the one for Amylin, not only inhibit abnormal protein formations but also have applications in mass spectrometry and enhancing receptor signaling in cells, showcasing the method's versatility for targeting flexible IDPs/IDRs.
Development of a Novel Assay for Direct Assessment of Selective Amylin Receptor Activation Reveals Novel Differences in Behavior of Selective and Nonselective Peptide Agonists.
Mol Pharmacol
April 2024
Drug Discovery Biology Theme (P.K., G.C., C.A.H., D.W., P.M.S.) and ARC Centre for Cryo-Electron Microscopy of Membrane Proteins (P.K., D.W., P.M.S.), Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia; and Research & Early Development, Novo Nordisk, Novo Nordisk Park, Maaloev, Denmark (T.G., B.B.-G.)
Dual amylin and calcitonin receptor agonists (DACRAs) show promise as efficacious therapeutics for treatment of metabolic disease, including obesity. However, differences in efficacy in vivo have been observed for individual DACRAs, indicating that detailed understanding of the pharmacology of these agents across target receptors is required for rational drug development. To date, such understanding has been hampered by lack of direct, subtype-selective, functional assays for the amylin receptors (AMYRs).
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