In Vitro: KPT-251 binds in the NES-binding groove, which is located on the central, convex side of the CRM1 ring. KPT-251 (72 h) suppresses melanoma cell proliferation. KPT-251 (1 μM; 0-48 h) modulates levels of p53, pRb, survivin, and ERK phosphorylation. KPT-251 (0.1 and 1 μM; 0-72 h) induces cell-cycle arrest and apoptosis.
In Vivo: 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. KPT-251 (50 mg/kg; p.o.; every other day for 21 days) suppresses tumor growth in mice melanoma xenograft models.