Description
Rigosertib sodium (ON-01910 sodium) is a multi-kinase inhibitor and a selective anti-cancer agent, which induces apoptosis by inhibition the PI3K/Akt pathway, promotes the phosphorylation of histone H2AX and induces G2/M arrest in cell cycle Rigosertib sodium is a selective and non-ATP-competitive inhibitor of PLK1 with an IC 50 of 9 nMIn VitroRigosertib is non-ATP-competitive inhibitor of PLK1 with IC 50 of 9 nM. Rigosertib also exhibits inhibition of PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC 50 of 18-260 nM. Rigosertib shows cell killing activity against 94 different tumor cell lines with IC 50 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. Rigosertib also inhibits several multidrug resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a, with IC 50 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. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoRigosertib (250 mg/kg, i.p.) markedly inhibits tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells. Rigosertib (200 mg/kg, i.p.) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell AssayTumor cells are plated into six-well dishes at a density of 1×10 5 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.IC50& Target:PLK1 9 nM (IC 50 ) PLK2 260 nM (IC 50 ) PDGFR 18 nM (IC 50 ) Src 155 nM (IC 50 ) BCR-ABL 32 nM (IC 50 ) Cdk1 260 nM (IC 50 ) Flt1 42 nM (IC 50 ) Fyn 182 nM (IC 50 )