BE-3-3-3-3

BE-3-3-3-3 (also known as BE3333 or 1,15-bis(ethylamino)-4,8,12-triazapentadecane) is a synthetic bis(ethyl) polyamine analogue under investigation as an antineoplastic agent, particularly for breast cancer, colon cancer, lung cancer, stomach cancer, and melanoma. Developed through academic collaborations involving Josai University, Chiba University, Rutgers University, and other institutions, BE-3-3-3-3 acts by disrupting cellular polyamine homeostasis. It inhibits key polyamine biosynthetic enzymes, including ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC), while strongly inducing the catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT). This leads to a depletion of natural polyamines (putrescine, spermidine, and spermine), inhibition of protein synthesis, and subsequent growth arrest. Additionally, BE-3-3-3-3 exhibits complex estrogen-mimetic activity at low concentrations by binding and activating estrogen receptor alpha (ERα) in the absence of estradiol, and it induces autophagy and apoptosis in cancer cells.

Other names

1,15-bis(ethylamino)-4,8,12-triazapentadecane1,15-bis(ethylamino)4,8,12-triazapentadecane3,7,11,15,19-pentazahenicosane