DKC1125 is a small molecule KSRP-binding compound that specifically inhibits the oncogenic KITENIN complex, suppresses distant metastasis of colorectal cancer (CRC).
DKC1125 specifically interacted with the binding pocket of the fourth KH-domain of KSRP.
DKC1125 degraded KITENIN and Dvl2 by recruiting RACK1 and miRNA-124, leading to the disintegration of the functional KITENIN–KSRP–RACK1–Dvl2 complex.
DKC1125 restored sensitivity to 5-fluorouracil, oxaliplatin, and cetuximab by normalizing expression of the deregulated microRNAs, including miRNA-124 in KITENIN-overexpressing CRC cells.
DKC1125 bound the KH-type splicing regulatory protein (KSRP), a downstream factor and stabilizer of the functional KITENIN complex, and specifically suppressed invasiveness of CRC cells expressing higher levels of KITENIN.
DKC1125 significantly inhibited the increase in cellular invasion caused by ectopic KITENIN expression in Caco2 cells, starting at a concentration of 0.5 uM.
DKC1125 inhibited the function of Dvl by interfering with the interaction of KSRP with Dvl2.