A Novel dual DYRK1A/B Inhibitor for the treatment of Type 1 Diabetes

Šarūnas Tumas¹Jonas Mingaila²Vytautas Baranauskas¹Emilija Baltrukonytė²Laurynas Orla¹Jan Aleksander Krasko³Roberta Pocevičiūtė¹Dina Berlina¹Alexei Belenky⁴Maria Vilenchik⁴Agnė Vaitkevičienė¹Olga Potapova¹Aurelijus Burokas^2*

• ¹Cureline Baltic UAB, Vilnius, Lithuania
• ²Life Sciences Center, Vilnius University, Vilnius, Lithuania
• ³Nacional Cancer Institute, Vilnius, Lithuania
• ⁴Felicitex therapeutics UAB, Vilnius, Lithuania

Type 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. In this study, we evaluate FX8474, a novel DYRK1 inhibitor, in a streptozotocin (STZ)-induced diabetic mouse model. Pharmacokinetic 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. These findings suggest that FX8474 has a modest effect on glucose regulation and immune cell composition, warranting further investigation into its potential therapeutic applications.