Supplementary file 1_A novel dual DYRK1A/B inhibitor for the treatment of type 1 diabetes.docx

BackgroundType 1 diabetes (T1D) is an autoimmune disease that leads to the progressive destruction of pancreatic β cells, resulting in insulin deficiency and hyperglycemia. Current treatments focus on insulin replacement, but novel therapeutic approaches targeting β cell regeneration are needed. Dual-specificity tyrosine-phosphorylation-regulated kinases 1A (DYRK1A) and 1B (DYRK1B) play key roles in cell cycle regulation and β cell proliferation.
MethodsIn this study, FX8474, a novel DYRK1 inhibitor, was evaluated in a streptozotocin (STZ)-induced diabetic mouse model. Mice were treated orally for 7 days, and pharmacokinetics, glucose regulation, and immune cell profiling were assessed.
ResultsPharmacokinetic analysis confirmed the oral bioavailability of FX8474, and treatment was associated with improved fasted glucose levels and glucose tolerance after a 7-day treatment. Immunophenotyping indicated that FX8474 treatment increases CD4+ memory T cell populations while decreasing CD4+ effector cells, as well as restores CD8+ T cell phenotypes to levels observed in healthy mice.
ConclusionFX8474 has a modest effect on glucose regulation and immune cell composition, warranting further investigation into its potential therapeutic applications.