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

Biological Activity

tasin-1 is a small molecule inhibitor of mutant adenomatous polyposis coli (apc) [1].adenomatous polyposis coli (apc) is a multifunctional tumor suppressor gene that is mutated in more than 80% of colon tumors. apc plays an important role in the negative regulation of canonical wnt signaling pathway through proteasomal degradation of b-catenin. apc is involved in cell cycle control, migration, differentiation, and apoptosis [1].tasin-1 is a selective inhibitor of mutant 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 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 [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 (wt apc) xenografts. in a genetically engineered crc mouse model, tasin-1 significantly reduced tumor formation in the colons of cpc;apc mice [1].1.lu zhang, panayotis c. theodoropoulos, ugur eskiocak, et al. selective targeting of mutant adenomatous polyposis coli (apc) in colorectal cancer. science translational medicine 19 oct 2016: vol. 8, issue 361, pp. 361ra140.