Leptomycin B  (Synonyms: CI 940; LMB)

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].

CRM1/exportin 1^[1]

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

540.73

<41°C Solid,>44°C Liquid

C₃₃H₄₈O₆

87081-35-4

O=C(O)/C=C(C)/C[C@H](C)[C@@H](O)[C@H](C)C([C@H](C)/C=C(C)/C=C/C[C@@H](C)/C=C(CC)\C=C\[C@H]1[C@@H](C)C=CC(O1)=O)=O

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

• [1]. N Kudo, et al. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9112-7.  [Content Brief]

  [2]. Sarah C Mutka,et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Res. 2009 Jan 15;69(2):510-7.  [Content Brief]

  [3]. Zhongwei Liu, et al.Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27.  [Content Brief]

  [4]. Sarah C Mutka, et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Res. 2009 Jan 15;69(2):510-7.  [Content Brief]