INCB13739
oral tissue-targeting 11β-HSD1 inhibitor Ph. II in T2DM/obesity completed (QD) scaffold-hopping from cortisone and prior 11β-HSD1 inh Bioorg. Med. Chem. Lett., August 1, 2022 Incyte Research Institute, Wilmington, DE
Other molecules you may be interested in
AZD4144
Recently, a surge of (pre)clinical compounds inhibiting the NLRP3 inflammasome, often featuring a hexahydroindacene ring system, has emerged, including Nodthera’s ND-0796. In a push for new chemotypes, AZ and Mitsubishi Tanabe have disclosed their clinical compound, AZD4144, which is currently in Ph. I trials in healthy volunteers. The discovery story detailed their efforts to overcome PLD (phospholipidosis), genotoxicity, and hERG inhibition in a non-classical pharmacophore series. The discovery was presented by Anders Johansson at the EFMC-ISMC 2024 Meeting in Rome.
"compound 6g"
“compound 6g” is an oral inhibitor of the sodium-glucose co-transporters (SGLTs) 1 and 2, intended for the treatment of hyperglycemia. SGLT2 selective inhibitors (gliflozins) are approved for treatment of type 2 diabetes, and an SGLT1/2 dual inhibitor is expected to result in greater glycemic control. Like other SGLT inhibitors, this molecule [...]
MK-0616
Merck’s macrocyclic PCSK9 protein-protein interaction (PPI) inhibitor, MK-0616, is a once-daily PCSK9-lowering and LDL-cholesterol-lowering small molecule that has recently demonstrated antibody-like efficacy as an oral agent in the clinic. The program highlights numerous technical achievements at the forefront of modern drug discovery, and will set a standard for modern “classics in drug discovery” for some time.
SCO-267
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 [...]
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.
