PCO371: The First Clinical Non-Peptide Class B GPCR Agonist and a “Molecular Wedge” Mechanism
PCO371
oral PTH1R agonist Ph. I for parathyroid hormone disorders; discontinued hit from functional screen vs. cells expressing hPTHR1 Nature, June 7, 2023 Chugai, Shizuoka, JP
Other molecules you may be interested in
danuglipron
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.
resmetirom
On Mar. 14th, 2024, resmetirom (REZDIFFRA™) became the first and only medicine approved by the FDA for the treatment of NASH (non-alcoholic steatohepatitis, aka MASH). Resmetirom, an oral, liver-targeting, once-daily THR-β-selective agonist originally discovered at Roche Nutley, was first highlighted as a Molecule of the Month in Dec. 2022. Now, with the FDA’s accelerated approval, this 2023 Molecule of the Year nominee reflects a historic milestone for liver drug discovery. This article reviews how the molecule works, how it was discovered, and why it’s a big deal.
seladelpar
In August 2024, seladelpar (LivdelziTM) became the first FDA-approved selective agonist of PPARδ (peroxisome proliferator-activated receptor δ), following an almost 20-year journey from the original discovery and patent publications. Originally developed by CymaBay in collaboration with Johnson & Johnson, approval was granted to Gilead Sciences following their February 2024 purchase of CymaBay Therapeutics for $4.3B. Seladelpar was approved as a second-line treatment for patients with primary biliary cholangitis.
GCC5694A
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 [...]
compound 10
“Compound 10” (AstraZeneca) is an oral CDK5-mediated PPARγ phosphorylation inhibitor and partial PPARγ agonist being developed as an antidiabetic drug . Although widely used PPARγ agonists such as rosiglitazone and pioglitazone are effective antidiabetics, they are limited by [...]