Rigosertib (ON-01910) is a selective, non-ATP-competitive PLK1 inhibitor (IC50: 9 nM) and multi-kinase inhibitor. As a selective anti-cancer agent, Rigosertib induces apoptosis by inhibiting the PI3 kinase/Akt pathway, promotes histone H2AX phosphorylation, and induces G2/M arrest in the cell cycle.

PLK1:9 nM, Src:155 nM, PLK2:260 nM, BCR-ABL:32 nM, CDK1:260 nM, Fyn:182 nM, FLK1:42 nM, PDGFR:18 nM

Rigosertib is a non-ATP-competitive inhibitor of PLK1 (IC50: 9 nM). Rigosertib displays cell killing activity against 94 different tumor cell lines (IC50: 50-250 nM), including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. Rigosertib also shows inhibition of PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1 (IC50: 18-260 nM). 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. Rigosertib also inhibits several multidrug-resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a (IC50: 50-100 nM). Rigosertib (100-250 nM) causes spindle abnormalities and apoptosis in HeLa cells. Rigosertib (0.25-5 μM) blocks cell cycle progression in G2/M phase in DU145 cells, causes an accumulation of cells containing subG1 content of DNA and activates apoptotic pathways. Rigosertib (50 nM-0.5 μM) induces loss of viability and caspase 3/7 activation in A549 cells. 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 the SDF-1-induced migration of leukemic cells[3][4][5].

Rigosertib (200 mg/kg, i.p.) displays inhibition on tumor growth in a mouse xenograft model of BT20 cells. Rigosertib (250 mg/kg, i.p.) markedly suppresses tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells [3][4].