AUTHOR=Tumas Šarūnas , Mingaila Jonas , Baranauskas Vytautas , Baltrukonytė Emilija , Orla Laurynas , Krasko Jan Aleksander , Pocevičiūtė Roberta , Berlina Dina , Belenky Alexei , Vilenchik Maria , Vaitkevičienė Agnė , Potapova Olga , Burokas Aurelijus 

TITLE=A novel dual DYRK1A/B inhibitor for the treatment of type 1 diabetes

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1657042

DOI=10.3389/fphar.2025.1657042

ISSN=1663-9812

ABSTRACT=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.