However, Leptomycin B's in vivo tolerance is limited, with a maximum tolerated dose (MTD) of 2.5 mg/kg when administered intravenously in HCT-116 tumor-bearing mice, indicating challenges in its therapeutic application due to off-target effects. Despite its potent inhibition of CRM1, the limited in vivo efficacy suggests the need for further refinement in targeting strategies to improve tolerance and efficacy^[4].

In vitro, Leptomycin B shows high potency against various cancer cell lines, with IC50 values ranging from 0.1 to 10 nM. Specifically, it inhibits SiHa, HCT-116, and SKNSH cells with IC50 values of 0.4, 0.3, and 0.4 nM, respectively, after 72 hours of exposure^[2].

Leptomycin B (LMB) (0.5 nM) has a synergistic effect on gefitinib (0-32 μM) -induced A549 and H460 cytotoxicity. Both gefitinib (0-32 μM) and Leptomycin B (0.5 nM) showed synergistic cytotoxic effects on A549 when treated for 24 and 48 h at the same time compared with gefitinib alone ^[3].