DCLK1-IN-1 is the first potent, selective inhibitor of the DCLK1 and DCLK2 kinases with IC50 of 9.5 nM and 31 nM in binding assays, respectively.
DCLK1-IN-1 exclusively inhibited DCLK1 and DCLK2 across a panel of 489 human kinases, significantly inhibited DCLK1, and weakly inhibited ERK5, in PATU-8988T cell lysates and live cells, did not inhibit any kinases under these conditions.
DCLK1-IN-1 displays pronounced on-target DCLK1 activity in vitro, and is suitable probe for in vivo evaluation.
Proteins associated with cell motility, including HN1, ZIP8 and FYN, were significantly downregulated after DCLK1-IN-1 treatment in the organoid cultures.
