KPT-251 is an orally active chromosome region maintenance 1 protein (CRM1) inhibitor. KPT-251 induces cancer cell apoptosis and shows antileukemic activity[1][2].
KPT-251 binds in the NES-binding groove, which is located on the central, convex side of the CRM1 ring[1].KPT-251 (72 h) suppresses melanoma cell proliferation[2].KPT-251 (1 μM; 0-48 h) modulates levels of p53, pRb, survivin, and ERK phosphorylation[2].KPT-251 (0.1 and 1 μM; 0-72 h) induces cell-cycle arrest and apoptosis[2].
KPT-251 (75 mg/kg/day; i.g.; three times per week for 5 weeks) effectively suppresses the growth of MV4-11 cells engrafted into NSG mice and provides a significant survival benefit[1].KPT-251 (50 mg/kg; p.o.; every other day for 21 days) suppresses tumor growth in mice melanoma xenograft models[2].
References:
[1]. Etchin J, et al. Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells. Leukemia. 2013 Jan;27(1):66-74.
[2]. Salas Fragomeni RA, et al. CRM1 and BRAF inhibition synergize and induce tumor regression in BRAF-mutant melanoma. Mol Cancer Ther. 2013 Jul;12(7):1171-9.