Leptomycin B

Leptomycin B (CI 940; LMB) is a potent inhibitor of the nuclear export of proteins. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue. Leptomycin B is a potent antifungal antibiotic blocking the eukaryotic cell cycle^[1]. IC50 & Target:CRM1/exportin 1^[1] In Vitro: Leptomycin B (LMB) is very potent in vitro against various cancer cell lines (IC50 values in the 0.1 to 10 nM range). Leptomycin B (LMB) inhibits SiHa, HCT-116, and SKNSH cells with IC₅₀s of 0.4, 0.3 and 0.4 nM for a 72 hour exposure, respectively^[2].
Leptomycin B (LMB) (0.5 nM) displays a synergistic effect on Gefitinib (0–32 μM)-induced cytotoxicity in A549 and H460 cell line. The simultaneous treatments of Gefitinib (0–32 μM) and Leptomycin B (0.5 nM) show synergistic cytotoxic effect on A549 as compared to Gefitinib alone at both 24 and 48 hours^[3]. In Vivo: Leptomycin B (LMB) is poorly tolerated in vivo. Maximum tolerated dose (MTD) is 2.5 mg/kg for LMB (single i.v.) in HCT-116 tumor–bearing mice.The limited in vivo efficacy of Leptomycin B is due to off-target effects because our nuclear export inhibitors (NEIs) retain the potent inhibition of CRM1, but are clearly better tolerated in vivo^[4].