Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Glucagon-like peptide-1 receptor (GLP-1R) is a well-established target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. The development of orally bioavailable and long-acting small-molecule GLP-1R agonists is a pursuit in both academia and industry. Herein, new selenium (Se)-containing compounds were designed using a Se-oxygen bioisostere strategy on the danuglipron scaffold. Among these, compound was orally bioavailable and exhibited full agonistic efficacy in promoting cyclic adenosine monophosphate (cAMP) accumulation. In hGLP-1R knock-in mice, effectively reduced blood glucose levels and food intake, with the duration of action slightly extended compared to that of danuglipron. Importantly, no significant adverse effects were observed in mice treated with during the subacute toxicity studies. This study delineates the potential of Se-containing compounds as orally bioavailable GLP-1R agonists, with compound emerging as a promising candidate for T2DM and obesity treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.4c02616 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioavailability of Oral Ondansetron in Dogs: A Crossover Study.
J Vet Pharmacol Ther
September 2025
Clinical Sciences Department, Colorado State University, Fort Collins, Colorado, USA.
The purpose of this study was to evaluate the pharmacokinetics of oral (PO) ondansetron compared to intravenous (IV) ondansetron in eight healthy client-owned dogs. Dogs were randomized to one of two protocols in a crossover design, receiving PO or IV ondansetron at a dose of 1 mg/kg on Day 0 and the opposite formulation at an equal dose on Day 7. Plasma was collected at baseline and 1, 2, 4, and 8 h post administration.
View Article and Find Full Text PDFDevelopment of benznidazole orally disintegrating tablets for paediatric patients.
J Pharm Pharmacol
September 2025
Facultad de Farmacia y Bioquímica, Departamento de Tecnología Farmacéutica, Cátedra de Tecnología Farmacéutica II, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina.
Objectives: To develop the orphan drug benznidazole (BNZ) in orally disintegrating tablets, for the neglected disease American Trypanosomiasis (Chagas disease) therapy. Although children are highly affected by this disease, there are no specific commercial pharmaceutical preparations for this age group in Argentina and in many other countries.
Methods: In the production process, co-milling in a ball mill was applied to enhance dissolution rates, followed by direct compression.
Quinoa protein-dextran conjugates as functional stabilizers for curcumin-loaded Nanoemulsions.
Food Res Int
November 2025
Fuzhou Institute of Oceanography, Minjiang University, Fuzhou 350108, China; Fujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Minjiang University, Fuzhou, China. Electronic address:
This study employed high-pressure microfluidization (HPM) to facilitate the Maillard reaction between quinoa protein (QP) and dextran (DX), systematically examining the effects of various pressures on the conjugate's physicochemical properties. Fourier transform infrared spectroscopy confirmed the formation of QP-DX conjugates, characterized by a new peak at 1149 cm (covalent CN bond). Secondary and tertiary structure analyses revealed that HPM-assisted Maillard reaction partially unfolded QP molecules, enhancing conformational flexibility and interfacial properties.
View Article and Find Full Text PDFThe Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor.
J Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
View Article and Find Full Text PDFProfile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as an tool compound for neuroinflammatory disorders.
RSC Med Chem
September 2025
NodThera Ltd. Suite 8, The Mansion, Chesterford Research Park, Little Chesterford, Saffron Walden Essex CB10 1XL UK
Inhibition of the NLRP3 inflammasome has emerged as a high potential treatment paradigm for the treatment of neuroinflammation, with demonstrated anti-neuroinflammatory effects in Parkinson's disease patients and a strong rationale in Alzheimer's disease and amyotrophic lateral sclerosis. To facilitate further progress in this field, brain penetrant NLRP3 inflammasome inhibitors as leads and tool compounds are required. We discovered a small molecule NLRP3 inflammasome inhibitor, NT-0527 (11), and extensively profiled this to reveal a highly potent, selective and brain penetrant compound.
View Article and Find Full Text PDF