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)	[1]: Interactive image
ChemSpider	5293927
IUPHAR/BPS	7833
KEGG	D10154
PubChem CID	6918736
SMILES [2]: 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 in development by Onconova Therapeutics. Riosertib is in phase III clinical trials for the treatment of chronic myelomonocytic leukemia.^[3]

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.^[4] 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 a non-ATP-competitive inhibitor. It inhibits PLK1 by competing at substrate-binding sites with an IC₅₀ of 9 nM.^[5]

References