2-Methoxyestradiol (2ME2) is a naturally occurring substance that is produced when the hormone estradiol is processed (metabolized) in the body. 2ME2 prevents both tumor growth (antiproliferative) and the formation of new blood vessels that tumors require to grow (antiangiogenic). Although 2ME2 is derived from estradiol, it binds poorly to estrogen receptors. On the contrary, it binds directly to a protein called tubulin, which is involved in cell division. This binding not only interferes with cell division (cell growth) but also inhibits hypoxia inducible factor-1 (HIF-1), an important factor for tumor cell survival. Additionally, 2ME2 has been reported to preferentially kill tumor cells, sparing normal cells, by causing reactive oxygen species (ROS) accumulation in cancer cells.
2ME2 under the trademark Panzem® (EntreMed Inc., Rockville, MD) is currently in Phase I/II clinical studies to investigate its safety and efficacy...