Context. GCC5694A (GC Pharma (Green Cross)) is an oral SGLT2 inhibitor. SGLT2 inhibitors help glycemic control in diabetes by preventing reabsorption of glucose in the kidney. Dapagliflozin was the first SGLT2 inhibitor approved in the EU (2012), and canagliflozin was the first to be approved in the US (2013). We recently highlighted [...]

SCO-267 is a full agonist of the GPCR GPR40, whose activation stimulates secretions of insulin and incretin. Since no crystal structures were available, the authors used conformational modeling to rationally improve the ligand from a weak lipophilic initial starting point (0.4 uM, clogP 9.4) to a more lipophilically efficient candidate (12 nM [...]

Peptidic GLP-1R agonists have received significant media coverage over the past year. Shortages of the semaglutide-based injectable diabetes medication Ozempic, which accounts for 40% of GLP-1R agonist US market share, have even emerged, driven by overwhelming demand for the weight loss formulation Wegovy, both for treatment of obesity and for short-term weight loss popularized by celebrities on social media. This article reviews the science of danuglipron, recent news, and what makes it different.

dotinurad (FYU-981) potently inhibits uric acid uptake by renal proximal tubule epithelial cells, increasing uric acid urinary secretion which can help hyperuricemic conditions like gout. The mechanism of action is believed to be inhibition of the URAT1 organic anion transporter which mediates uric acid reabsorption. Benzbromarone has been [...]

Orforglipron is an oral non-peptide glucagon-like peptide-1 (GLP-1) receptor partial agonist that entered Ph. III for obesity and type-2-diabetes mellitus (T2DM). This 2020 and 2023 Molecule of the Year nominee (nominated initially back when it was still in Ph. I) was first discovered by Chugai Pharmaceuticals under the name OWL833, then licensed by Eli Lilly for worldwide development under the name LY3502970. The article discusses where it sits in the GLP-1R agonist landscape, why it’s scientifically notable, how it works with illustrations from cryo-EM structures, its synthesis, and more.