Biological Activity
kpt-185 is a selective and irreversible inhibitor of chromosome maintenance protein 1 (crm1) with ic50 values of 100-500nm [1].crm1 is an important nuclear protein export receptor. blocking crm1-mediated nuclear export can result in the suppression of tumors. as an inhibitor of crm1, kpt-185 binds crm1within the cys528 site and prevents crm1from interacting with tumor-suppressor proteins. in the in vitro studies on aml cell lines, kpt-185 inhibits proliferation of a variety of leukemia cells with ic50 values ranging from 100nm to 500nm. it induces cell-cycle arrest at g1 and induces apoptosis. kpt-185 also strongly affects cell colony formation. in addition, the inhibition of crm1 caused by kpt-185 induces differentiation of aml blast. besides that, kpt-185 is also found to inhibit proliferation and induce apoptosis of pancreatic cancer cells including colo-357, hpac and bxpc-3 [1, 2].
References
[1] ranganathan p, yu x, na c, et al. preclinical activity of a novel crm1 inhibitor in acute myeloid leukemia. blood, 2012, 120(9): 1765-1773.
[2] azmi a s, aboukameel a, bao b, et al. selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. gastroenterology, 2013, 144(2): 447-456.
