CAS號	87081-35-4	產(chǎn)地	國產(chǎn)
規(guī)格	1 mg	級別	化工級
證書	ISO系列證書

Leptomycin B (Synonyms: 來普霉素B; CI 940; LMB)

Leptomycin B (CI 940; LMB) 是一種蛋白出核轉(zhuǎn)運(yùn)抑制劑。Leptomycin 通過半胱an酸殘基處的共價修飾使 CRM1/exportin 1 失活。

生物活性

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]

體外研究(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].

Cell Viability Assay^[3]

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.

體內(nèi)研究(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].

分子量：540.73

Formula：C₃₃H₄₈O₆

CAS 號：87081-35-4

中文名稱：來普霉素B；細(xì)霉素B

運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.

儲存方式

-20°C, stored under nitrogen

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

溶解性數(shù)據(jù)

In Vitro:

DMSO : 100 mg/mL (184.94 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

配制儲備液

濃度溶劑體積質(zhì)量	1 mg	5 mg	10 mg

1 mM	1.8494 mL	9.2468 mL	18.4935 mL
5 mM	0.3699 mL	1.8494 mL	3.6987 mL
10 mM	0.1849 mL	0.9247 mL	1.8494 mL

請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 儲存時，請在 6 個月內(nèi)使用，-20°C 儲存時，請在 1 個月內(nèi)使用。

In Vivo:

以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：

——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用；以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

1.

請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (4.62 mM); Clear solution
2.

請依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 2.5 mg/mL (4.62 mM); Suspended solution; Need ultrasonic
3.

請依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.62 mM); Clear solution

參考文獻(xiàn)

[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]

注：產(chǎn)品僅用于科研