PROTAC TTK degrader-2 is a potent TTK (threonine tyrosine kinase) PROTAC degrader, with DC 50 values of 3.1 and 12.4 nM in COLO-205 and HCT-116 cell, respectively. PROTAC TTK degrader-2 exhibits target degradation and anticancer efficacy in a xenograft mouse model of COLO-205 human colorectal cancer cells.