Rigosertib sodium

Uses

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[1][2]. Rigosertib sodium is a selective and non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM[3].

Definition

ChEBI: Rigosertib sodium is the sodium salt of rigosertib. It is an anti-cancer agent which has been granted Orphan Drug Designation by the FDA for use in patients with myelodysplastic syndromes (MDS). It has a role as a microtubule-destabilising agent, an antineoplastic agent, an EC 2.7.11.21 (polo kinase) inhibitor and an apoptosis inducer. It contains a rigosertib(1-).

Biological Activity

Cell permeable: yes', 'Primary Target
PI 3-K/Akt/mTOR signaling', 'Target IC50: 32, 42, 182, 18 and 155 nM against Bcr-Abl, Flt1, Fyn, PDGFR, and Src, respectively

in vivo

IC 50

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)

References

[1] Xu F, et al. Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signalingtransduction pathways in high-grade myelodysplastic syndrome. Sci Rep. 2014 Dec 4;4:7310. DOI:10.1038/srep07310
[2] Hyoda T, et al. Rigosertib induces cell death of a myelodysplastic syndrome-derived cell line by DNA damage-induced G2/M arrest. Cancer Sci. 2015 Mar;106(3):287-93. DOI:10.1111/cas.12605
[3] 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. DOI:10.1016/j.ccr.2005.02.009
[4] 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. DOI:10.1021/jm200570p
[5] 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 DOI:10.1158/1078-0432.CCR-11-2113