FINEMENT

Non disponible en dehors du Royaume-Uni et de l'Irlande

Biochem/physiol Actions

FINDY is a structural analog of RD0392, a canonical ATP-competitive inhibitor of mature dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).

FINDY is a cell-permeable thioxothiazolidinone derivative that specifically targets newly synthesized cellular DYRK1A, but not DYRK1B or DYRK2, for proteasomal degradation by suppressing DYKR1A intramolecular Ser97 autophosphorylation, a necessary event for folding/maturation of newly translated DYRK1A. Unlike INDY and other ATP-competitive DYRK inhibitors, FINDY is ineffective against the kinase activity of DYRK1A, DYRK1B, DYRK2, or DYRK3 (IC50 >10 µM) and inhibits only five kinases (GSK3β, MARK4, PIM1, PIM3, PLK3) by over 75% at 10 µM among a panel of 271 other kinases. FINDY (2.5 µM) is shown to selectively rescue the developmental defect of Xenopus embryos induced by the overexpression of DYRK1A, but not DYRK1B, while INDY prodrug (2.5 µM) treatment indiscriminately prevents defect caused by both DYRK1A and DYRK1B expression.

Packaging

5, 25 mg in glass bottle