Rigosertib (ON-01910)

Mouse (female athymic, NCR-nu/nu) xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells

ON-01910 is currently under a Phase III clinical trial in refractory myelodysplastic syndrome patients with excess blasts.

ON-01910 (Estybon, Novonex, Rigosertib) is a non-ATP-competitive inhibitor of PLK1 (Polo-like kinase 1) with IC50 of 9 nM.

Dissolved in PBS

ON-01910 is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. ON-01910 also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18–260 nM. ON-01910 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, ON-01910 has little or no effect unless its concentration is greater than 5–10 uM. In HeLa cells, ON-01910 (100–250 nM) induces spindle abnormalities and apoptosis. [1] ON-01910 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, ON-01910 (0.25–5 uM) 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, ON-01910 (50 nM–0.5 uM) induces loss of viability and caspase 3/7 activa recent study, ON-01910 induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. ON-01910 also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells. [3]

96 hours

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 x 105cells/mL/well, and ON-01910 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.

ON-01910 Chemical Structure

, , Dr Antonino Maria Sparta, PhD University of Bologna, ON-01910purchased from Selleck

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO