CaNDY is a highly potent rectifier of the aberrant splicing, potently inhibits DYRK1A, DYRK1B, CLK1/CLK2 with IC50 of 21.6/68.3/116 nM in in vitro kinase assays.
CaNDY is a potent and selective inhibitor of DYRK family kinases, CaNDY induces selective degradation of DYRK1A, and inhibits catalytic activity of recombinant DYRK1A with IC50 value of 7.9 nM by competing with ATP, antagonizes the CDC37 interaction with DYRK1A.
CaNDY demonstrated CFTR pseudo exon suppression with EC50 of 1.2 uM, 20.4 times lower than that of TG003.
Splice modulation by CaNDY is mediated by its CLK-inhibition activity.
CaNDY, but not CFTR modulator VX-809, rescues mature CFTR expression from the CFTR gene with the 3,849 + 10 kb C>T mutation, suppresses SRSF phosphorylation.
CaNDY (3 uM) treatment rescued CFTR channel activity from CFTRC>T-GFP at an extent comparable to that of CFTRWT-GFP, demonstrating a restoration of functional CFTR expression.