Rigosertib is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. Rigosertib also exhibits inhibition against 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. 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. In a recent study, Rigosertib induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells.
(E/Z)-Rigosertib sodium 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SKNAS cells
2 µM
24 hours
Decreased microtubule stability
Mol Cancer Ther. 2021 Feb;20(2):307-319.
RD cells
2 µM
48 hours
Induced apoptosis
Mol Cancer Ther. 2021 Feb;20(2):307-319.
SMS-CTR cells
2 µM
48 hours
Induced apoptosis
Mol Cancer Ther. 2021 Feb;20(2):307-319.
HCC1806 cells
200 nM
Induced cell death
JCI Insight. 2024 May 30;9(13):e174329.
Huh7 cells
0.1 to 0.5 µM
Inhibition of HCV replication
Proc Natl Acad Sci U S A. 2022 Dec 20;119(51):e2214911119.
HeLa and C33A cells
>0.5 µM
24 hours
Rigosertib induces G2/M arrest and enhances susceptibility to radiation therapy.
Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):1180-7.
DLD1 and HCT116 cells
1 µM
24 hours
To determine the cytotoxic effects and apoptosis induction. RGS significantly induced apoptosis in both DLD1 and HCT116 cells.
Cancer Biol Med. 2021 Aug 4;19(2):213–28.
HCC1806 cells
150 nM
Induced phosphorylation of histone H3 and G2/M cell cycle arrest
JCI Insight. 2024 May 30;9(13):e174329.
(E/Z)-Rigosertib sodium 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
KRAS-mutant colorectal cancer patient-derived xenograft models
Intraperitoneal injection
100 mg/kg
3 weeks
To evaluate the inhibitory efficacy on tumor growth. RGS showed a stronger therapeutic effect than the combination standard therapy involving fluoropyrimidine + oxaliplatin/irinotecan + bevacizumab.
Cancer Biol Med. 2021 Aug 4;19(2):213–28.
Mice
Subcutaneous xenograft model of HCV replicon-harboring Huh7 cells
Intraperitoneal injection
150 mg/kg
Single dose, observed after 24 hours
To validate the anti-HCV activity of rigosertib in vivo
Proc Natl Acad Sci U S A. 2022 Dec 20;119(51):e2214911119.
SCID-Beige mice
RD xenograft model
Intraperitoneal injection
150 mg/kg
Twice daily, 5 days per week, until study endpoint
Delayed tumor growth and prolonged survival
Mol Cancer Ther. 2021 Feb;20(2):307-319.
Mice
Human cervical carcinoma xenografts
Intraperitoneal injection
200 mg/kg
3 doses in the first 36 hours and then 2 more doses during radiation therapy
Rigosertib, combined with irradiation, showed superior tumor growth delay compared to cisplatin.
Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):1180-7.
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