TASIN-1 Hydrochloride (Truncated APC Selective INhibitor-1) is a nove, potent and selective small molecule inhibitor of mutant adenomatous polyposis coli (APC). It acts by selectively killing colorectal cancer cells that express truncated APC by reducing cellular cholesterol levels and inducing apoptotic cell death through the ER stress/ROS/JNK signaling in colon cancer cells. In two authentic human CRC cell lines HCT116 (WT APC) and DLD1
(truncated APC1417), TASIN-1 exhibited potent and selective toxicity
toward DLD1 cells with IC50 value of 70 nM but not toward HCT116 cells
(IC50 >50 μM). TASIN-1 also reduced the endogenous cholesterol
biosynthesis rate. TASIN-1 exerted its killing effects primarily by
depleting cholesterol through inhibition of emopamil-binding protein
(EBP) activity. However, knockdown of truncated APC (>90%) expression
desensitized DLD1 cells to TASIN-1, suggesting that APC is required for
TASIN-1’s cytotoxicity.