Leptomycin B

Leptomycin B is a highly specific inhibitor of the export protein CRM1, with IC50 values ranging from 0.1 to 10 nM against various cancer cell lines [1]. 

The exportin CRM1 is absolutely required for the nuclear export of a wide variety of cancer-related “cargo” proteins including p53, c-Abl, and FOXO-3A, cytoplasmic localization of which may result in uncontrolled growth and the onset of disease [1]. 

In 15 sarcoma cell lines with varied histological backgrounds, Leptomycin B showed tumor inhibitory effects, with the average IC50 of 4.23 nM [2]. In A549 cells, Leptomycin B at the concentration of 50 nM, caused CRM1 to redistribute from the nucleus to the cytoplasm [3]. 

In SiHa tumor–bearing mice, Leptomycin B (25 mg/kg, i.v., one dose per 7 days, for a total of three doses) only exhibited grow delay effects, which was consistent with the limited in vivo efficacy previously observed for Leptomycin B. In addition, Leptomycin B was also found to be relatively toxic, compared to the Leptomycin B analog [1]. 

References:

[1]. Mutka S C, Yang W Q, Dong S D, et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Research, 2009, 69(2): 510-517.

[2]. Qiao Z, Kondo T. Screening of a growth inhibitor library of sarcoma cell lines to identify potent anti-cancer drugs. Journal of Electrophoresis, 2019, 63: 1-7.

[3]. Rahmani K, Dean D A. Leptomycin B alters the subcellular distribution of CRM1 (Exportin 1). Biochem Biophys Res Commun. 2017, 488(2): 253-258.