Rigosertib

Rigosertib

Names
IUPAC name 2‐[(2‐Methoxy‐5‐{[(E)‐2‐(2,4,6‐trimethoxyphenyl)ethenesulfonyl]methyl}phenyl)amino]acetic acid
Other names ON-01910
Identifiers
CAS Number	1225497-78-8
3D model (JSmol)	Interactive image
ChemSpider	5293927
PubChem CID	6918736
CompTox Dashboard (EPA)	DTXSID30207984
SMILES COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
Properties
Chemical formula	C21H25NO8S
Molar mass	451.49 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Rigosertib (ON-01910 sodium salt, with Estybon as trade name) is a synthetic benzyl styryl sulfone that is in phase III clinical trials as an anti-cancer agent. Its geometrical isomer (Z)-ON 01910·Na has less cytotoxicity on cancer cells.

Mechanism

Rigosertib is a small molecule inhibitor, which simultaneously inhibits PI3K and PLK signaling pathways.The over-expression of these two pathways may lead occurrence and development of many kinds of tumors. Thus rigosertib performs potential antineoplastic activity in multiple tumor types.

Rigosertib can convert the gene express profilings, cause mitotic cell-cycle G2 arrest of tumor cells, leading their apoptosis. And what it causes in normal cells is a reversible cell arrest at the G1 and G2 stage without apoptosis. Rigosertib shows little liver damage or neurotoxicity in mouse xenograft models.

Rigosertib is an non-ATP-competitive inhibitor. It inhibits PLK1 by competing at substrate-binding sites with an IC₅₀ of 9 nM.