XPO1-IN-1

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

XPO1-IN-1 

XPO1-IN-1 (compound D4) 是一种口服有效的 XPO1 抑制剂, 其在 MM.1S 细胞中的 IC50 为 24 nM。XPO1-IN-1 能有效诱导细胞凋亡和细胞周期阻滞。XPO1-IN-1 具有良好的代谢稳定性和药代动力学性质。XPO1-IN-1 可用于多发性骨髓瘤的研究。

XPO1-IN-1

XPO1-IN-1 Chemical Structure

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生物活性

XPO1-IN-1 (compound D4) is an orally active and potent XPO1 inhibitor, with an IC50 of 24 nM in MM.1S cell. XPO1-IN-1 can efficiently induce cell apoptosis and cell cycle arrest. XPO1-IN-1 displays favorable metabolic stability and pharmacokinetic properties. XPO1-IN-1 can be used for multiple myeloma (MM) research[1].

IC50 & Target

XPO1

 

体外研究
(In Vitro)

XPO1-IN-1 (compound D4) (24 h) shows high anti-proliferation efficacy in MM.1S cell and lymphomatous cell lines[1].
XPO1-IN-1 (0-10 μM, 24 h) induces cancer cell cycle arrest[1].
XPO1-IN-1 (0-10 μM, 48 h) induces apoptosis of MM.1S cell[1].
XPO1-IN-1 (0-10 μM, 2 h) inhibits XPO1-dependent nuclear export[1].
XPO1-IN-1 shows the good metabolic stability, with more than 80% intact compound remained over rat plasma (2 h), and around 85% intact compound remained in liver microsomes (1 h)[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

Cell Line: MM.1S, Mino, VAL, Rael, Namaiwa, Mutu, H9, JB6, and YT[1]
Concentration:
Incubation Time: 24 h
Result: Showed high anti-proliferation efficacy in MM.1S cell and lymphomatous cell lines (Mino, VAL, Rael, Namaiwa, Mutu, H9, JB6, and YT), with IC50 values of 24, 80.2, 189.1, 201.8, 77.7, 158.2, 101.1, 154.1, and 75.4 nM, respectively.

Cell Cycle Analysis

Cell Line: MM.1S cell[1]
Concentration: 0, 0.1, 1, 5, and 10 μM
Incubation Time: 24 h
Result: Induced cancer cell cycle arrest in high concentration (>100 nM), increased the population of cells arrested in G2 to 37.3% in 5 μM.

Apoptosis Analysis

Cell Line: MM.1S cell[1]
Concentration: 0, 0.1, 1, and 10 μM
Incubation Time: 48 h
Result: Induced apoptosis, significantly increased the apoptotic cell rate to 64.7% (10 μM) when compared to the sample with negative control (6.7%).

Immunofluorescence

Cell Line: MM.1S cell[1]
Concentration: 0, 0.1, 1, and 10 μM
Incubation Time: 2 h
Result: Inhibited XPO1-dependent nuclear export.

体内研究
(In Vivo)

XPO1-IN-1 (compound D4) (Sprague Dawley rats; 10 mg/kg, IG; 1 mg/kg, IV; once) shows a good pharmacokinetic properties[1]. Pharmacokinetic Parameters of XPO1-IN-1 in SD rats[1].

Parameters i.g. (10 mg/kg) i.v. (1 mg/kg)
Tmax (h) 2.17 ± 1.76 0.08
T1/2 (h) 2.12 ± 0.16 2.32 ± 0.17
Cmax (ng/mL) 1391.27 ± 586.77 1239.08 ± 152.54
AUC0-t (ng/mL·h) 5774.13 ± 1461.41 1668.03 ± 229.48
AUC0-∞ (ng/mL·h) 6387.17 ± 1637.18 1791.40 ± 236.56
CL (mL/h/kg) 1638.65 ± 431.97 565.30 ± 80.40
F (%) 34.6

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Sprague Dawley rats[1]
Dosage: 10 mg/kg (IG), 1 mg/kg (IV)
Administration: Oral gavage (IG), IV, once (Pharmacokinetic Analysis)
Result: Showed a good pharmacokinetic properties, with relatively long half-life of 2.12 h (IG) and 2.32 h (IV), respectively, and decent bioavailability F (%) of 34.6%.

分子量

519.42

Formula

C20H15F6N5O3S

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.

参考文献
  • [1]. Qu B, et al. Design, synthesis and biological evaluation of sulfonamides inhibitors of XPO1 displaying activity against multiple myeloma cells. Eur J Med Chem. 2022;235:114257.

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