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 (compound D4) is an orally active and potent XPO1 inhibitor, with an IC 50 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].

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]. 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 IC 50 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.

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) T max (h) 2.17 ± 1.76 0.08 T 1/2 (h) 2.12 ± 0.16 2.32 ± 0.17 C max (ng/mL) 1391.27 ± 586.77 1239.08 ± 152.54 AUC 0-t (ng/mL·h) 5774.13 ± 1461.41 1668.03 ± 229.48 AUC 0-∞ (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 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%.

C20H15F6N5O3S

519.42

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years