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
1225497-78-8
3D model (Jmol) [1]: Interactive image
ChEMBL ChEMBL1241855
ChEMBL2013119
ChemSpider 5293927
7833
PubChem 6918736
Properties
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.[3] 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.[4]

References

  1. "physical and chemical data on chemispider website".
  2. "physical and chemical data on chemispider website".
  3. Nuthalapati S (Sep 2012). "Preclinical pharmacokinetic and pharmacodynamic evaluation of novel anticancer agents, ON01910.Na (Rigosertib, Estybon™) and ON013105, for brain tumor chemotherapy.". Pharm Res. 29 (9). doi:10.1007/s11095-012-0780-y. PMID 22678771.
  4. "Rigosertib activity data in vitro and in vivo". selleckchemicals. 20 Aug 2014.


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