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Selinexor (KPT-330) is a first-in-class, oral, selective inhibitor of Nuclear Export (SINE) compound, works by binding to and inhibiting the nuclear export protein XPO1 (also known as CRM1). KPT-330 (Selinexor; ATG-010) exhibits similar effects on the viability of T-ALL cells and elicits rapid apoptotic response. KPT-330 reduces cell growth in MOLT-4, Jurkat, HBP-ALL, KOPTK-1, SKW-3, and DND-41 cell lines, with IC50 values of 34-203 nM. A study demonstrated striking in vivo activity of KPT-330 against T-ALL and AML cells, with little toxicity to normal murine haematopoietic cells.
J Cell Mol Med. 2022 May;26(9):2646-2657.
Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia
Selinexor purchased from AbMole
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Source | Cell Death Discov (2018). Figure 2. KPT-330 |
| Method | MTS assay | |
| Cell Lines | K562 and K562G cells | |
| Concentrations | 0.1 nM | |
| Incubation Time | 24, 48 and 72 h | |
| Results | KPT-330 inhibited proliferation of K562 and K562G cells in a time and dosedependent manner, as shown in the morphology analysis (data not shown) and MTS assay |
| Cell Experiment | |
|---|---|
| Cell lines | MOLT-4, Jurkat, HBP-ALL, KOPTK-1, SKW-3, and DND-41 cell lines |
| Preparation method | Culturing cell lines in RPMI 1640 medium, supplemented with 10% fetal bovine serum and penicillin/streptomycin.Using cell Titer Glo assay to assess cell viability upon treatment with either dimethyl sulfoxide (DMSO) or KPT-330. Plating cells at a density of 10 000 cells per well in a 96-well plate and incubating them with DMSO or increasing concentrations of KPT-330. After 72 h exposure to KPT-330 ,mearsuring the cell viability and reporting as a percentage of DMSO control cells. Jurkat cells that overexpress BCL2 are generated using MSCV-IRES-GFP retroviral expression system. Jurkat cells infected with BCL2 or control vector viruses are sorted by flow cytometry and the expression of BCL2 confirmed by Western blot analysis using BCL2 antibody |
| Concentrations | ~1 μM |
| Incubation time | 72 hours |
| Animal Experiment | |
|---|---|
| Animal models | T-ALL and AML orthograft mouse model |
| Formulation | Pluronic F-68/PVP-K29/32 |
| Dosages | 20 -25 mg/kg |
| Administration | p.o. |
| Molecular Weight | 443.31 |
| Formula | C17H11F6N7O |
| CAS Number | 1393477-72-9 |
| Solubility (25°C) | DMSO 50 mg/mL Ethanol 30 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related CRM1 Products |
|---|
| Eltanexor
Eltanexor, also known as KPT-8602, is a second-generation exportin-1 (CRM1) inhibitor with IC50 values of 20−211 nM in 10 AML lines. |
| Felezonexor (CBS9106)
Felezonexor (CBS9106; SL-801) is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity without affecting CRM1 mRNA levels. Felezonexor is also a reversible inhibitor of XPO1, inhibits nuclear export by covalently binding to Cys528 as well as by inducing the degradation of XPO1. |
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