BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A); glycogen synthase kinase 3β (GSK3β)

January 7, 2016 8:00 AM UTC

In vitro, rodent and human tissue studies suggest dual inhibitors of GSK3β and DYRK1A could increase β cell mass to help treat diabetes. Chemical synthesis of aminopyrazine analogs and testing in cultured mouse β cells and primary mouse, rat and human primary islets identified a compound that increased β cell proliferation compared with vehicle, without impairing insulin secretion. In primary rat islets treated with the compound, overexpression of GSK3β or DYRK1A decreased β cell proliferation compared with unmodified expression of GSK3β or DYRK1A. In a mouse model of Type I diabetes, the compound or combined inhibition of GSK3β and DYRK1A with tool compounds increased glucose tolerance, β cell proliferation and β cell mass compared with vehicle or either tool compound alone. Next steps could include developing more selective dual inhibitors of DYRK1A and GSK3β.

Pharmasum Therapeutics A/S has the DYRK1A inhibitor PST-900 in discovery to treat Alzheimer's disease (AD). ...