Publications by authors named "K W Sloop"
Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.
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- * Researchers developed a new glucagon receptor agonist, LY3324954, that has better potency and effectiveness compared to regular glucagon, and it showed a prolonged impact in various animal models.
- * In tests, LY3324954 led to increased energy expenditure, weight loss, and better fat management in diet-induced obese mice, indicating its potential as a therapeutic option for obesity-related conditions.
Article Synopsis
- GLP-1 receptor agonists are effective for treating type 2 diabetes and obesity, but patient responses vary due to genetic differences.
- A specific genetic variant (A316T) shows protective effects against T2D and cardiovascular disease and leads to improved blood glucose and insulin levels in a mouse model.
- However, this variant results in reduced effectiveness when using GLP-1R agonist medications, highlighting the need to understand genetic variations for personalized treatment strategies.
Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease.
Am J Physiol Endocrinol Metab
November 2024
The secretin-like, class B1 subfamily of seven transmembrane-spanning G protein-coupled receptors (GPCRs) consists of 15 members that coordinate important physiological processes. These receptors bind peptide ligands and use a distinct mechanism of activation that is driven by evolutionarily conserved structural features. For the class B1 receptors, the C-terminus of the cognate ligand is initially recognized by the receptor via an N-terminal extracellular domain that forms a hydrophobic ligand-binding groove.
View Article and Find Full Text PDFIntroduction: We assessed the effect of the prandial state on the pharmacokinetics, safety, and tolerability of single and multiple doses of orforglipron (LY3502970), an oral, non-peptide glucagon-like peptide 1 receptor agonist (GLP-1 RA), in two studies (A and B).
Methods: Study A and study B were phase 1, randomized, crossover studies in healthy adults aged 18-65 years and 21-70 years, respectively. Participants received single (3 mg, study A) or multiple (16 mg, study B) oral doses of orforglipron under fasted and fed conditions.