Leptomycin B

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Leptomycin B 是一种有效的蛋白质核输出抑制剂，也是一种有效的抗真菌抗生素，可阻断真核细胞周期。 Leptomycin B 通过半胱氨酸残基的共价修饰使 CRM1/exportin 1 失活。

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.

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 AssayCell Line:The non-small cell lung cancer (NSCLC) cell lines A549 and H460 Concentration:0.5 nMIncubation 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.

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.

CI 940 | LMB

Membrane Transporter/Ion Channel

CRM1

CRM1|exportin 1

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87081-35-4

540.73

C33H48O6

>98% (HPLC)

In Vitro:?DMSO : ≥ 100 mg/mL (184.94 mM)

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(-20℃)

With Ice Pack

≥ 2 years