1507367-37-4

FINDY is a cell-permeable thioxothiazolidinone derivative th at specifically targets newly synthesized cellular DYRK1Abut not DYRK1B or DYRK2for proteasomal degradation by suppressing DYKR1A intramolecular Ser97 autophosphorylationa necessary event for folding/maturation of newly translated DYRK1A. Unlike INDY and other ATP-competitive DYRK inhibitorsFINDY is ineffective against the kinase activity of DYRK1ADYRK1BDYRK2or DYRK3 (IC50 >10 μM) and inhibits only five kinases (GSK3βMARK4PIM1PIM3PLK3) 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 DYRK1Abut not DYRK1Bwhile INDY prodrug (2.5 μM) treatment indiscriminately prevents defect caused by both DYRK1A and DYRK1B expression.''FINDY is a structural analog of RD0392a canonical ATP-competitive inhibitor of mature dual-specificity tyrosine phosphorylati