592542-60-4
592542-60-4 structure
- Name: Rigosertib sodium
- Chemical Name: Sodium {[2-methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfo nyl}methyl)phenyl]amino}acetate
- CAS Number: 592542-60-4
- Molecular Formula: C21H24NNaO8S
- Molecular Weight: 473.47200
- Catalog: Signaling Pathways Cell Cycle/DNA Damage Polo-like Kinase (PLK)
- Create Date: 2018-09-11 18:11:24
- Modify Date: 2024-01-02 15:26:53
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Rigosertib (sodium) is a non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM, and shows 30-fold selectivity over PLK2.
| Name | Sodium {[2-methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfo nyl}methyl)phenyl]amino}acetate |
|---|---|
| Synonyms |
Sodium {[2-methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfonyl}methyl)phenyl]amino}acetate
Glycine,N-[2-methoxy-5-[[[(1E)-2-(2,4,6-trimethoxyphenyl) ethenyl]sulfonyl] methyl]phenyl]-,sodium Slat Rigosertib sodium ON-01910.Na Glycine, N-[2-methoxy-5-[[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl]methyl]phenyl]-, sodium salt (1:1) Rigosertib (sodium) |
| Description | Rigosertib (sodium) is a non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM, and shows 30-fold selectivity over PLK2. |
|---|---|
| Related Catalog | |
| Target |
PLK1:9 nM (IC50) PLK2:260 nM (IC50) PDGFR:18 nM (IC50) Src:155 nM (IC50) BCR-ABL:32 nM (IC50) Cdk1:260 nM (IC50) Flt1:42 nM (IC50) Fyn:182 nM (IC50) |
| In Vitro | Rigosertib is non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM. Rigosertib also exhibits inhibition of PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18-260 nM. Rigosertib shows cell killing activity against 94 different tumor cell lines with IC50 of 50-250 nM, including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. While in normal cells, such as HFL, PrEC, HMEC, and HUVEC, Rigosertib has little or no effect unless its concentration is greater than 5-10 μM. In HeLa cells, Rigosertib (100-250 nM) induces spindle abnormalities and apoptosis[1]. Rigosertib also inhibits several multidrug resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a, with IC50 of 50-100 nM. In DU145 cells, Rigosertib (0.25-5 μM) blocks cell cycle progression in G2/M phase, results in an accumulation of cells containing subG1 content of DNA, and activates apoptotic pathways. In A549 cells, Rigosertib (50 nM-0.5 μM) induces loss of viability and caspase 3/7 activation[2]. Rigosertib sodium (2 μM) induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib sodium (2 μM) also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells[3]. |
| In Vivo | Rigosertib (250 mg/kg, i.p.) markedly inhibits tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells[1]. Rigosertib (200 mg/kg, i.p.) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells[2]. |
| Kinase Assay | Recombinant PLK1 (10 ng) is incubated with different concentrations of Rigosertib in a 15 µL reaction mixture (50 mM HEPES, 10 mM MgCl2, 1 mM EDTA, 2 mM Dithiothreitol, 0.01% NP-40 [pH 7.5]) for 30 min at room temperature. Kinase reactions are performed for 20 min at 30°C in a volume of 20 µL (15 µL enzyme + inhibitor, 2 µL 1 mM ATP), 2 µL of γ32P-ATP (40 μCi), and 1 µL of recombinant Cdc25C (100 ng) or casein (1 μg) substrates. Reactions are terminated by boiling for 2 min in 20 µL of 2× Laemmli buffer. Phosphorylated substrates are separated by 18% SDS-PAGE. The gels are dried and exposed to X-ray film for 3-10 min. |
| Cell Assay | Cells are grown in either DMEM or RPMI supplemented with 10% fetal bovine serum and 1 unit/mL penicillin-streptomycin solution. Tumor cells are plated into six-well dishes at a density of 1×105 cells/mL/well, and Rigosertib is added 24 hours later at various concentrations. Cell counts are determined from duplicate wells after 96-hour of treatment. The total number of viable cells is determined by trypan blue exclusion. |
| Animal Admin | Bel-7402 tumor models: twenty female athymic (NCR-nu/nu) nude mice are injected with 1 × 107 Bel-7402 tumor cells subcutaneously, and 10-14 days later, when the tumor volumes reach 200-250 mm, the mice are divided into four groups such that each group harbors tumors of the same volume. Rigosertib (ON01910, 250 mg/kg) dissolved in PBS is administered alone or in combination with oxaliplatin (100 mg/kg) intraperitonially on alternate days. Tumor measurements are done two times/week using traceable digital vernier calipers. Body weight is determined during each measurement. The animals are observed for signs of toxicity[1]. |
| References |
| Molecular Formula | C21H24NNaO8S |
|---|---|
| Molecular Weight | 473.47200 |
| Exact Mass | 473.11200 |
| PSA | 131.60000 |
| LogP | 2.62230 |
| Storage condition | 2-8℃ |