Leptomycin B

SKU: orb1217555

Description

Leptomycin B is a potent inhibitor of the nuclear export of proteins and is a potent antifungal antibiotic blocking the eukaryotic cell cycle. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue.

Key Properties

• CAS Number: 87081-35-4
• MW: 540.73
• Purity: >98% (HPLC)
• Formula: C₃₃H₄₈O₆
• SMILES: CC/C(/C=C/[C@@H]([C@@H](C)C=C1)OC1=O)=C/[C@H](C)C/C=C/C(/C)=C/[C@@H](C)C([C@@H](C)[C@@H]([C@@H](C)C/C(/C)=C/C(O)=O)O)=O
• Target: CRM1
• Solubility: In Vitro: DMSO : ≥ 100 mg/mL (184.94 mM)

Bioactivity

• 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.
• 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. 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. Cell Viability Assay Cell line: The non-small cell lung cancer (NSCLC) cell lines A549 and H460. Concentration: 0.5 nM Incubation time: 24 and 48 hours. Result: The IC50 of Gefitinib at 48 hours was 32.0±2.5 μM while it was significantly reduced to 25.0±2.1 μM with the combination of 0.5 nM Leptomycin B. The significant synergistic cytotoxic effect from co-treatment of 0.5 nM Leptomycin B with Gefitinib was also confirmed in H460 cell line. Cell Viability Assay Cell line: A549. Concentration: 0.5 nM Incubation time: 48 hours. Result: 0.5 nM Leptomycin B plus Gefitinib or Gefitinib alone had a decreased p-EGFR(Tyr1068) expressions compared with controls. p-Akt (Ser473) was inhibited in a dose-response manner by Gefitinib treatments, but it was enhanced by gefitinib+Leptomycin B co-treatments compared with gefitinib alone. A549 treated by Gefitinib+Leptomycin B had a higher expression of p-Erk1/2(Thr202/Tyr204) than A549 treated by Gefitinib alone.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CI 940 | LMB

Quick Database Links

Gene Symbol

CRM1