Dyr726 is a potent, selective and brain-penetrant inhibitor of PI3Kα with IC50 of 3.6 nM, >1,000-fold selective against the β and γ-PI3K isoforms.
Dyr726 also inhibits common PI3Kα activating mutants, E542K, E545K, and H1047R with IC50s of 5nM, 3.8nM, and 15.7nM respectively.
Dyr726 inhibits the oncogenic PI3K-AKT-mTOR signaling pathway with complete ablation of phospho-AKT, phospho-PRAS40, and phospho-S6K in primary patient derived GBM6 cells.
Dyr726 is a very potent inhibitor of the type III RTKs PDGFRA/B, KIT and FLT3, inhibits PDGFRA at 62nM, PDGFRB at 76nM, KIT at 13nM, and FLT3 at 55nM.
Dyr726 targets oncogenic gain-of-function mutants of PDGFRA and PI3Kα.
Dyr726 is a very potent inhibitor of the DYRK and CLK family of CMGC kinases with biochemical IC50s of less than 100 nM for all isoforms except CLK3 (277 nM).
Dyr726 kills WNT-dependent cancer organoids and extends survival of tumour mice in vivo.