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592542-59-1

592542-59-1 structure
592542-59-1 structure
  • Name: Rigosertib
  • Chemical Name: 2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid
  • CAS Number: 592542-59-1
  • Molecular Formula: C21H25NO8S
  • Molecular Weight: 451.49000
  • Catalog: Signaling Pathways Cell Cycle/DNA Damage Polo-like Kinase (PLK)
  • Create Date: 2018-03-29 08:00:00
  • Modify Date: 2024-01-02 09:17:01
  • Rigosertib 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
Synonyms 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
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

[1]. Gumireddy K, et al. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005 Mar;7(3):275-86.

[2]. Reddy MV, et al. Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): synthesis, structure-activity relationship, and biological activity. J Med Chem.

[3]. Chapman CM, et al. ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91.

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)

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title: CAS No. 592542-59-1 | Chemsrc address: https://www.chemsrc.com/en/baike/347669.html

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