GNF-4877

A Dyrk1a and Gsk3ß inhibitor (IC50s = 6 and 16 nM, respectively, for the mouse enzymes), selective for Dyrk1a and Gsk3ß over a panel of 57 kinases but does inhibit 10 other kinases at 1 µM, increases the proliferation of R7T1 mouse pancreatic ß-cells and primary human pancreatic ß-cells (EC50s = 0.66 and 0.54 µM, respectively), increases the number of islet and ß-cells and the levels of total DNA and ATP in primary human islet cells at 2 µM, increases the proliferation of transplanted primary human islet cells and decreases the levels of blood glucose in mice at 50 mg/kg twice per day, reduces the levels of blood glucose in an OGTT in a transgenic RIP-DTA mouse model of type I diabetes at 50 mg/kg twice per day, increases the mass of, and levels of insulin in, pancreatic ß-cells in the same mice. Formulation: A solid. InChI: InChI=1S/C25H27FN6O4/c1-14(2)36-16-5-6-18(26)17(10-16)19-12-29-23(27)22(30-19)24(33)31-20-11-28-8-7-21(20)32-9-3-4-15(13-32)25(34)35/h5-8,10-12,14-15H,3-4,9,13H2,1-2H3,(H2,27,29)(H,31,33)(H,34,35)/t15-/m1/s1. InChIKey: UZIATSFXNVOVFE-OAHLLOKOSA-N. SMILES: O=C(C1=NC(C2=CC(OC(C)C)=CC=C2F)=CN=C1N)NC3=CN=CC=C3N4C[C@@H](CCC4)C(O)=O