A creative tour de force in molecular design in this article "GLP-1R–GIPR–PPARα/γ/δ

A creative tour de force in molecular design in this article "GLP-1R–GIPR–PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice" by Timo Müller and a team the includes Jonathan Douros and Patrick Knerr, PhD, now at the Indiana Biosciences Research Institute (IBRI) (+ Stephanie Mowery, I don't know you but hi there!). A quintuple agonist, FIVE different targets at the same time (GLP-1R–GIPR-PPARα-PPARγ-PPARδ), in ONE molecule. The real beauty here is not just connecting lanifibranor (a triple PPAR agonist) to a GLP-1R-GIPR agonist but to also enable its targeted delivery into GLP-1R- and GIPR-expressing cells. The results in mice: it "outperforms GLP-1R–GIPR co-agonism and semaglutide, further decreasing body weight, food intake and hyperglycaemia in obese and insulin-resistant mice through synergistic incretin and PPAR action. The metabolic action of GLP-1–GIP–lanifibranor is blunted in mice with genetic or pharmacological inhibition of GLP-1R, GIPR or PPARδ and is absent in DIO double incretin receptor-knockout mice, collectively suggesting that GLP-1–GIP–lanifibranor has substantial therapeutic value in the treatment of obesity and diabetes." Just beautiful!