Rigosertib
Modify Date: 2024-01-02 09:17:01
Rigosertib structure
|
Common Name | Rigosertib | ||
|---|---|---|---|---|
| CAS Number | 592542-59-1 | Molecular Weight | 451.49000 | |
| Density | 1.332±0.06 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C21H25NO8S | Melting Point | 172-174 ºC (acetone ) | |
| MSDS | N/A | Flash Point | N/A | |
Use of RigosertibRigosertib is a non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM, and shows 30-fold greater selectivity against PLK2. |
| Name | 2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid |
|---|---|
| Synonym | More Synonyms |
| Description | Rigosertib is a non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM, and shows 30-fold greater selectivity against 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 |
| Density | 1.332±0.06 g/cm3 |
|---|---|
| Melting Point | 172-174 ºC (acetone ) |
| Molecular Formula | C21H25NO8S |
| Molecular Weight | 451.49000 |
| Exact Mass | 451.13000 |
| PSA | 128.77000 |
| LogP | 3.95700 |
| Storage condition | 2-8℃ |
| Water Solubility | Practically insoluble (0.011 g/L) (25 ºC) |
CAS#:61010-34-2
CAS#:22216-44-0![[(4-Methoxy-3-nitrobenzyl)sulfonyl]acetic acid Structure](https://image.chemsrc.com/caspic/006/592542-51-3.png)
CAS#:592542-51-3
CAS#:592542-50-2
CAS#:119-10-8
CAS#:41870-24-0
CAS#:31680-08-7| 1910 Na |
| Glycine, N-[2-methoxy-5-[[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl]methyl]phenyl]- |
| UNII-67DOW7F9GL |
| N-[2-Methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfonyl}methyl)phenyl]glycine |
| Rigosertib |