TASIN-1 是截短的APC基因（结肠腺瘤样息肉基因）选择性抑制剂，可以抑制胆固醇生物合成并发挥细胞毒性作用。它是一种预防和干预APC突变型结直肠癌的潜在治疗策略。

TASIN-1 is a small molecule inhibitor of mutant adenomatous polyposis coli (APC).

In two authentic human CRC cell lines HCT116 (WT APC) and DLD1 (truncated APC1417), TASIN-1 exhibited potent and selective toxicity toward DLD1 cells (IC50: 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 [1].

In nude mice with established DLD1 and HT29 tumors, intraperitoneal injection of TASIN-1 twice daily for 18 days reduced the size of tumor xenografts and tumor growth rates. TASIN-1 resulted in the appearance of apoptotic cells with fragmented nuclei and induced an increase in cleaved caspase 3 and cleaved PARP1. However, TASIN-1 did not inhibit tumor growth in HCT116 xenografts. In a genetically engineered CRC mouse model, TASIN-1 significantly reduced tumor formation in the colons of CPC [1].

792927-06-1

C18H28N2O3S

352.49

塔辛-1;1-[(4-methoxyphenyl)sulfonyl]-4'-methyl-4,1'-bipiperidine

EtOH:12.02 mg/mL (with ultrasonic)
H2O:2.45 mg/mL (with gentle warming and ultrasonic)
DMSO:35.2 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years