KPT-251

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

一种小分子选择性核输出抑制剂（CRM1 抑制剂；SINE），具有有效的抗白血病活性。

A small-molecule, selective inhibitor of nuclear export (CRM1 inhibitor;SINE) that exhibits potent antileukemic activity; induces apoptosis at nanomolar concentrations in a panel of human AML cell lines with negligible toxicity to normal hematopoietic cells.

KPT-251 binds in the NES-binding groove, which is located on the central, convex side of the CRM1 ring.KPT-251 (72 h) suppresses melanoma cell proliferation.KPT-251 (1 μM; 0-48 h) modulates levels of p53, pRb, survivin, and ERK phosphorylation.KPT-251 (0.1 and 1 μM; 0-72 h) induces cell-cycle arrest and apoptosis.Western Blot Analysis 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 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 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.

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.KPT-251 (50 mg/kg; p.o.; every other day for 21 days) suppresses tumor growth in mice melanoma xenograft models. Animal Model:7-weekold female NOD-SCID-IL2Rcγnull (NSG) mice, introduced 2 × 106 luciferase-expressing MV4-11 cells via tail-vein injectionsDosage: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 Dosage:50 mg/kg Administration:Oral, every other day for 21 days Result:Suppressed tumor growth, increased cleaved caspase-3 and decreased Ki67.

KPT 251 | KPT251

Membrane Transporter/Ion Channel

Exportin-1

Exportin-1

——

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1388841-50-6

375.23

C14H7F6N5O

>98% (HPLC)

——

FC(C1=CC(C(F)(F)F)=CC(C2=NN(/C=C\C3=NN=CO3)C=N2)=C1)(F)F

2-[(1Z)-2-[3-[3,5-Bis(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl]ethenyl]-1,3,4-oxadiazole

(-20℃)

With Ice Pack

≥ 2 years