CLK

CLK inhibitors block cell division cycle-like kinases (CLKs), which control pre-mRNA splicing in the nucleus. The four human members, CLK1 to CLK4, are dual-specificity kinases closely related to the DYRK family. They phosphorylate serine/arginine-rich (SR) splicing factors and so change where these factors sit in the nucleus and which splice sites are used. The benzothiazole TG003 was introduced as a CLK inhibitor that shifts alternative splicing in cells. CLK-IN-T3 later revealed a role of CLK activity in exon recognition and in the formation of conjoined gene transcripts. The listed compounds include (E/Z)-TG003, CLK-IN-T3, T025 and the CLK4 inhibitor ML167.