Rigosertib: Difference between revisions

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
CAS Number	592542-59-1 ;
3D model (JSmol)	: Interactive image;
ChEBI	CHEBI:145417;
ChEMBL	ChEMBL1241855; ChEMBL2013119;
ChemSpider	5293927;
IUPHAR/BPS	7833;
KEGG	D10154;
PubChem CID	6918736;
UNII	67DOW7F9GL ;
CompTox Dashboard (EPA)	DTXSID30207984 ;
	InChI 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;
	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

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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

Rigosertib is a microtubule-destabilizing agent.^[4]

References

^ "physical and chemical data on chemispider website".
^ "Onconova Therapeutics". Retrieved 2019-04-26.
^ "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.
^ 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.

This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it.

[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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@@ Line 2: / Line 2: @@
 | Name = Rigosertib
 | ImageFile = Rigosertib.svg
+| ImageAlt =
-|  ImageSize = 200px
+| IUPACName = (2-Methoxy-5-<nowiki/>{[(''E'')-2-(2,4,6-trimethoxyphenyl)ethene-1-sulfonyl]methyl}phenyl)glycine
-|  ImageAlt =
-| IUPACName = 2‐[(2‐Methoxy‐5‐{[(''E'')‐2‐(2,4,6‐trimethoxyphenyl)ethenesulfonyl]methyl}phenyl)amino]acetic acid
+| SystematicName = (2-Methoxy-5-<nowiki/>{[(''E'')-2-(2,4,6-trimethoxyphenyl)ethene-1-sulfonyl]methyl}anilino)acetate
 | OtherNames = ON-01910
-| Section1 = {{Chembox Identifiers
+|Section1={{Chembox Identifiers
+| IUPHAR_ligand = 7833
-|   CASNo = 1225497-78-8
+| CASNo_Ref = {{cascite|correct|CAS}}
-|   PubChem = 6918736
+| CASNo = 592542-59-1
-|   ChemSpiderID = 5293927
+| UNII_Ref = {{fdacite|correct|FDA}}
-|   SMILES = COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
+| UNII = 67DOW7F9GL
-|   SMILES_Ref = <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> }}
+| PubChem = 6918736
-| Section2 = {{Chembox Properties
+| ChEBI = 145417
-|   C=21|H=25|N=1|O=8|S=1
-|   Appearance =
+| ChemSpiderID = 5293927
-|   Density =
+| ChEMBL = 1241855
-|   MeltingPt =
+| ChEMBL2 = 2013119
-|   BoilingPt =
+| 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
-|   Solubility =  }}
+| 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>
-| Section3 = {{Chembox Hazards
+| 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+
-|   MainHazards =
+| StdInChIKey = OWBFCJROIKNMGD-BQYQJAHWSA-N
-|   FlashPt =
+}}
-|   Autoignition =  }}
+|Section2={{Chembox Properties
+| C=21 | H=25 | N=1 | O=8 | S=1
+| Appearance =
+| Density =
+| MeltingPt =
+| BoilingPt =
+| Solubility = }}
+|Section3={{Chembox Hazards
+| MainHazards =
+| FlashPt =
+| 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.  Its [[geometrical isomer]] (''Z'')-ON 01910·Na has less cytotoxicity on cancer cells.
+'''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.
 ==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>{{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 ==
 {{reflist}}
-[[category:Antineoplastic and immunomodulating drug stubs]]
+[[Category:Antineoplastic and immunomodulating drugs]]
+[[Category:Experimental cancer drugs]]
 {{antineoplastic-drug-stub}}