Biological Characterization of 8-Cyclopropyl-2-(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-one, a Promising Inhibitor of DYRK1A

Corinne Fruit (1) , Florence Couly (1) , Rahul Bhansali (2) , Malini Rammohan (2) , Mattias F. Lindberg (3) , John d. Crispino (2, 4) , Laurent Meijer (3) , Thierry Besson (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 The University of Chicago Medicine [Chicago]
3 ManRos Therapeutics
4 Northwestern University Feinberg School of Medicine

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-one (also called FC162) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610).

Keywords: quiescence; thiazolo[5; 4-f]quinazolin-9(8H)-one; CMGC kinases; DYRK family kinases; pre-B cells; SH-SY5Y-Tau-4R cells

Domains: Chemical Sciences

Corinne Fruit, Florence Couly, Rahul Bhansali, Malini Rammohan, Mattias F. Lindberg, et al.. Biological Characterization of 8-Cyclopropyl-2-(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-one, a Promising Inhibitor of DYRK1A. Pharmaceuticals, 2019, 12 (4), pp.185. ⟨10.3390/ph12040185⟩. ⟨hal-02417254⟩