TASIN-1 (hydrochloride)

TASIN-1 hydrochloride is a selective inhibitor of truncated APCTR (adenomatous polyposis coli gene) that exerts cytotoxic effects by inhibiting cholesterol biosynthesis. TASIN-1 hydrochloride specifically targets colorectal cancer (CRC) cells carrying APC truncated mutations, while having no significant toxicity to wild-type APC cells. TASIN-1 hydrochloride exerts cytotoxic effects by targeting Emopamil binding protein (EBP) to inhibit cholesterol biosynthesis, triggering endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) generation, and JNK-mediated apoptosis, and inhibiting Akt survival signaling. TASIN-1 hydrochloride can be used to prevent and intervene in APC mutant colorectal cancer. In Vitro:TASIN-1 hydrochloride selectively inhibits adenomatous polyposis coli truncated (APC^TR) in DLD1 cells with IC₅=70 nM^[1].
TASIN-1 hydrochloride (70 nM; 72 h) significantly inhibits the proliferation of human colon cancer cells DLD1 (APC^TR) with IC₅₀ of 70 nM, and has a high selectivity against HCT116 (APC^WT) cells with IC₅₀ >50 μM^[1].
TASIN-1 hydrochloride (2.5 μM; 7 d) inhibits soft agar colony formation of DLD1 cells, but has no significant effect on HCT116^[1].
TASIN-1 hydrochloride (2.5 μM; 2-48 h) reduced the cholesterol synthesis rate and endogenous cholesterol levels in DLD1 cells, but had no effect on HCT116 cells^[1].
TASIN-1 hydrochloride (2.5 μM; 24 h) induced the expression of endoplasmic reticulum stress marker CHOP and JNK phosphorylation, and activated caspase 3/7 activity in DLD1 cells, but no significant changes were observed in HCT116 cells^[2].
In Vivo:TASIN-1 (40 mg/kg; ip; twice daily; 18 days) hydrochloride significantly inhibits tumor growth and induced tumor cell apoptosis in the nude mouse DLD1/HT29 (APC^TR) subcutaneous xenograft model, without inhibitory effect on HCT116 (APC^WT) tumors^[1].
TASIN-1 (20, 40 mg/kg; ip; twice weekly; 90 or 100 days) hydrochloride reduces the number and size of colon polyps and inhibits tumor progression in the CPC;Apc mouse genetic colorectal cancer model without significant liver and kidney damage or weight loss^[1].