KPT-251 是一种具有口服活性的染色体区域维持1蛋白 (CRM1) 抑制剂。 KPT-251 诱导癌细胞凋亡 (apoptosis)，具有抗白血病活性。
| 生物活性 | KPT-251 is an orally active chromosome region maintenance 1 protein (CRM1) inhibitor. KPT-251 inducescancercellapoptosisand shows antileukemic activity[1][2]. |
体外研究
(In Vitro) | KPT-251 binds in the NES-binding groove, which is located on the central, convex side of the CRM1 ring[1].
KPT-251 (72 h) suppresses melanoma cell proliferation[2].
KPT-251 (1 μM; 0-48 h) modulates levels of p53, pRb, survivin, and ERK phosphorylation[2].
KPT-251 (0.1 and 1 μM; 0-72 h) induces cell-cycle arrest and apoptosis[2].
Western Blot Analysis[2] | Cell Line: | Melanoma BRAF WT (Mewo) and mutant cells (A375) | | Concentration: | 1 μM | | Incubation Time: | 4, 8, 24 and 48 h | | Result: | Prevented cytoplasmic p53 degradation, decreased survivin levels, increased ERK phosphorylation in both BRAF WT and mutant and reduced pRb and p-pRb levels. |
Cell Cycle Analysis[2] | Cell Line: | Mewo and A375 cells | | Concentration: | 1 μM | | Incubation Time: | 24, 48 and 72 h | | Result: | Reduced S-phase, both G1 and/or G2 cell-cycle arrest can be observed. |
Apoptosis Analysis[2] | Cell Line: | Mel-Juso, SK-MEL-28, SK-MEL-5 and A375 cells | | Concentration: | 0.1 and 1 μM | | Incubation Time: | 24, 48 and 72 h | | Result: | Increased caspase-3 and -7 activity in the tested melanoma cell lines in a dose- and time-related manner. |
|
体内研究
(In Vivo) | KPT-251 (75 mg/kg/day; i.g.; three times per week for 5 weeks) effectively suppresses the growth of MV4-11 cells engrafted into NSG mice and provides a significant survival benefit[1].
KPT-251 (50 mg/kg; p.o.; every other day for 21 days) suppresses tumor growth in mice melanoma xenograft models[2].
| Animal Model: | 7-weekold female NOD-SCID-IL2Rcγnull(NSG) mice, introduced 2 × 106luciferase-expressing MV4-11 cells via tail-vein injections[1] | | Dosage: | 75 mg/kg/day | | Administration: | Gavage, three times per week for 5 weeks | | Result: | Exhibited significantly increased survival with leukemia progression occurring only after cessation of treatment, prevented infiltration of leukemia cells into mouse bone marrow and spleen, and spared normal hematopoietic cells. |
| Animal Model: | Athymic nude mice Nu/Nu, melanoma xenograft models[2] | | Dosage: | 50 mg/kg | | Administration: | Oral, every other day for 21 days | | Result: | Suppressed tumor growth, increased cleaved caspase-3 and decreased Ki67. |
|
| 分子量 | |
| Formula | |
| CAS 号 | |
| 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. |
m.cnreagent.com