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| Name = Rigosertib
| Name = Rigosertib
| ImageFile = Rigosertib.svg
| ImageFile = Rigosertib.svg
| ImageAlt =
| ImageAlt =
| IUPACName = 2‐[(2‐Methoxy‐5‐{[(''E'')‐2‐(2,4,6‐trimethoxyphenyl)ethenesulfonyl]methyl}phenyl)amino]acetic acid
| IUPACName = (2-Methoxy-5-<nowiki/>{[(''E'')-2-(2,4,6-trimethoxyphenyl)ethene-1-sulfonyl]methyl}phenyl)glycine
| SystematicName = (2-Methoxy-5-<nowiki/>{[(''E'')-2-(2,4,6-trimethoxyphenyl)ethene-1-sulfonyl]methyl}anilino)acetate
| OtherNames = ON-01910
| OtherNames = ON-01910
|Section1={{Chembox Identifiers
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 7833
| IUPHAR_ligand = 7833
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 1225497-78-8
| CASNo = 592542-59-1
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 67DOW7F9GL
| PubChem = 6918736
| PubChem = 6918736
| ChEBI = 145417
| ChemSpiderID = 5293927
| ChemSpiderID = 5293927
| ChEMBL = 1241855
| ChEMBL = 1241855
| ChEMBL2 = 2013119
| ChEMBL2 = 2013119
| KEGG = D10154
| SMILES = COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
| SMILES = COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
| SMILES_Comment = <ref>{{cite web|url=http://www.chemspider.com/Chemical-Structure.5293927.html?rid=536d329b-927e-45a8-8495-63b421e6eba5|title=physical and chemical data on chemispider website}}</ref>
| SMILES_Comment = <ref>{{cite web|url=http://www.chemspider.com/Chemical-Structure.5293927.html?rid=536d329b-927e-45a8-8495-63b421e6eba5|title=physical and chemical data on chemispider website}}</ref>
| StdInChI=1S/C21H25NO8S/c1-27-15-10-19(29-3)16(20(11-15)30-4)7-8-31(25,26)13-14-5-6-18(28-2)17(9-14)22-12-21(23)24/h5-11,22H,12-13H2,1-4H3,(H,23,24)/b8-7+
| StdInChIKey = OWBFCJROIKNMGD-BQYQJAHWSA-N
}}
}}
|Section2={{Chembox Properties
|Section2={{Chembox Properties
| C=21 | H=25 | N=1 | O=8 | S=1
| C=21 | H=25 | N=1 | O=8 | S=1
| Appearance =
| Appearance =
| Density =
| Density =
| MeltingPt =
| MeltingPt =
| BoilingPt =
| BoilingPt =
| Solubility = }}
| Solubility = }}
|Section3={{Chembox Hazards
|Section3={{Chembox Hazards
| MainHazards =
| MainHazards =
| FlashPt =
| FlashPt =
| AutoignitionPt = }}
| AutoignitionPt = }}
}}
}}


'''Rigosertib''' ('''ON-01910''' sodium salt, with '''Estybon''' as trade name) is a synthetic benzyl styryl sulfone that is in [[phase III clinical trial]]s as an anti-cancer agent.{{cn|date=April 2016}}
'''Rigosertib''' ('''ON-01910''' sodium salt, with '''Estybon''' as trade name) is a synthetic benzyl styryl sulfone in development by [[Onconova Therapeutics]].<ref>{{Cite web|url=https://finpedia.co/bin/Companies/Onconova%20Therapeutics/|title=Onconova Therapeutics|access-date=2019-04-26}}</ref> Rigosertib is in [[phase III clinical trial]]s for the treatment of [[chronic myelomonocytic leukemia]].<ref>{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT01928537|title = Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients with Myelodysplastic Syndrome with Excess Blasts Progressing on or After Azacitidine or Decitabine|date = 29 June 2020}}</ref>


Its [[geometrical isomer]] (''Z'')-ON 01910·Na has less cytotoxicity on cancer cells.
Its [[geometrical isomer]] (''Z'')-ON 01910·Na has less cytotoxicity on cancer cells.


==Mechanism==
==Mechanism==
Rigosertib is a [[microtubule]]-destabilizing agent.<ref>{{cite journal|last1=Jost|first1=M|title=Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent|journal=Molecular Cell|volume=68 |issue=1|pages=210–223.e6|pmid=28985505|pmc=5640507|url=|year=2017|doi=10.1016/j.molcel.2017.09.012}}</ref>
Rigosertib is a small molecule inhibitor, which simultaneously inhibits [[PI3K]] and [[PLK1|PLK]] signaling pathways.The over-expression of these two pathways may lead occurrence and development of many kinds of [[cancer|tumors]].<ref name=Nuthalapati2012>{{cite journal|title=Preclinical pharmacokinetic and pharmacodynamic evaluation of novel anticancer agents, ON01910.Na (Rigosertib, Estybon™) and ON013105, for brain tumor chemotherapy.|author=Nuthalapati S|doi=10.1007/s11095-012-0780-y|volume=29|issue=9|date=Sep 2012|journal=Pharm Res| pmid=22678771}}</ref> Thus rigosertib performs potential antineoplastic activity in multiple tumor types.

Rigosertib can convert the [[Gene expression profiling|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|IC<sub>50</sub>]] of 9 nM.<ref>{{cite web|title=Rigosertib activity data in vitro and in vivo|url=http://www.selleckchem.com/products/ON-01910.html|publisher=selleckchemicals|date=20 Aug 2014}}</ref>


== References ==
== References ==
{{reflist}}
{{reflist}}


[[Category:Antineoplastic and immunomodulating drug stubs]]
[[Category:Antineoplastic and immunomodulating drugs]]
[[Category:Antineoplastic and immunomodulating drugs]]
[[Category:Experimental cancer drugs]]
[[Category:Experimental cancer drugs]]

Latest revision as of 00:11, 7 May 2023

Rigosertib
Names
IUPAC name
(2-Methoxy-5-{[(E)-2-(2,4,6-trimethoxyphenyl)ethene-1-sulfonyl]methyl}phenyl)glycine
Systematic IUPAC name
(2-Methoxy-5-{[(E)-2-(2,4,6-trimethoxyphenyl)ethene-1-sulfonyl]methyl}anilino)acetate
Other names
ON-01910
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1S/C21H25NO8S/c1-27-15-10-19(29-3)16(20(11-15)30-4)7-8-31(25,26)13-14-5-6-18(28-2)17(9-14)22-12-21(23)24/h5-11,22H,12-13H2,1-4H3,(H,23,24)/b8-7+
    Key: OWBFCJROIKNMGD-BQYQJAHWSA-N
  • [1]: COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
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).

Rigosertib (ON-01910 sodium salt, with Estybon as trade name) is a synthetic benzyl styryl sulfone in development by Onconova Therapeutics.[2] Rigosertib 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

[edit]

Rigosertib is a microtubule-destabilizing agent.[4]

References

[edit]
  1. ^ "physical and chemical data on chemispider website".
  2. ^ "Onconova Therapeutics". Retrieved 2019-04-26.
  3. ^ "Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients with Myelodysplastic Syndrome with Excess Blasts Progressing on or After Azacitidine or Decitabine". 29 June 2020.
  4. ^ Jost, M (2017). "Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent". Molecular Cell. 68 (1): 210–223.e6. doi:10.1016/j.molcel.2017.09.012. PMC 5640507. PMID 28985505.


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