Rigosertib sodium
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MedKoo CAT#: 202080

CAS#: 1225497-78-8 (sodium)

Description: Rigosertib (ON-01910 sodium salt) is a synthetic benzyl styryl sulfone analogue with potential antineoplastic activity. Polo-like kinase 1 inhibitor ON 01910.Na inhibits polo-like kinase1 (Plk1), inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. This agent may exhibit synergistic antitumor activity in combination with other chemotherapeutic agents. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner. Note: this product is supplied as sodium salt.

Chemical Structure

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Rigosertib sodium
CAS# 1225497-78-8 (sodium)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 202080
Name: Rigosertib sodium
CAS#: 1225497-78-8 (sodium)
Chemical Formula: C21H25NO8S
Exact Mass: 451.13
Molecular Weight: 451.490
Elemental Analysis: C, 55.86; H, 5.58; N, 3.10; O, 28.35; S, 7.10

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3850 Ready to ship
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Related CAS #: 592542-59-1 (free base)   1225497-78-8 (sodium)   592542-60-4 (sodium)  

Synonym: ON01910; ON 01910; ON-01910; Rigosertib sodium; brand name: Estybon.

IUPAC/Chemical Name: sodium (E)-2-((2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)phenyl)amino)acetate

InChi Key: VLQLUZFVFXYXQE-USRGLUTNSA-M

InChi Code: InChI=1S/C21H25NO8S.Na/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);/q;+1/p-1/b8-7+;

SMILES Code: O=C([O-])CNC1=CC(CS(=O)(/C=C/C2=C(OC)C=C(OC)C=C2OC)=O)=CC=C1OC.[Na+]

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in water.

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:   Related CAS# 1225497-78-8 (sodium salt); 592542-59-1 (free acid)    

Biological target: Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay.
In vitro activity: Rigosertib induced caspase 3/7 activity (Fig. 2A) and phosphatidylserine externalization as detected by annexin V staining (Fig. 2B) in RAS-mutant RMS cell lines, RD and SMS-CTR, suggesting apoptosis was induced in these cells. Caspase 3/7 activity was also induced by rigosertib in RAS WT FN-RMS cell lines, RMS-YM and RH18 (Supplementary Fig. S1A), as well as RAS mutant (SKNAS and NBEB) and RAS WT (SHEP and SY5Y) NB cell lines (Supplementary Fig. S1B). However, rigosertib also induced G2–M arrest in RMS and NB cells, as determined by DNA content analysis (Fig. 2C), suggesting that the rigosertib effects in these cell lines are both cytotoxic and cytostatic. Reference: Mol Cancer Ther. 2021 Feb;20(2):307-319. https://mct.aacrjournals.org/content/20/2/307.long
In vivo activity: To evaluate the effects of rigosertib on sepsis in vivo, this study administrated rigosertib in mice 2 h before inducing the sepsis. This study detected quick mice death in PBS-treated mice after LPS treatment. In contrast, mice pretreated with rigosertib had decreased mortality when compared to PBS pretreated mice. Obvious inflammation and inflammatory cell infiltration in the lung of septic mice pretreated with PBS were detected (Figure 5B). In contrast, there was much less inflammation and inflammatory cell infiltration in the lung of septic mice pretreated with rigosertib. Moreover, septic mice pretreated with rigosertib had a significantly lower level of IL-6, TNF-α, and IL-1β in serum than septic mice pretreated with PBS (Figure 5C). These findings indicated that rigosertib ameliorated LPS-induced sepsis in mice. Reference: Immun Inflamm Dis. 2021 Jun 1. https://onlinelibrary.wiley.com/doi/10.1002/iid3.458

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 62.0 137.32
DMSO:PBS (pH 7.2) (1:6) 0.1 0.31
DMF 30.0 66.45
Water 94.0 208.20

Preparing Stock Solutions

The following data is based on the product molecular weight 451.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Kowalczyk JT, Wan X, Hernandez ER, Luo R, Lyons GC, Wilson KM, Gallardo DC, Isanogle KA, Robinson CM, Mendoza A, Heske CM, Chen JQ, Luo X, Kelly AE, Difilippantinio S, Robey RW, Thomas CJ, Sackett DL, Morrison DK, Randazzo PA, Jenkins LMM, Yohe ME. Rigosertib Induces Mitotic Arrest and Apoptosis in RAS-Mutated Rhabdomyosarcoma and Neuroblastoma. Mol Cancer Ther. 2021 Feb;20(2):307-319. doi: 10.1158/1535-7163.MCT-20-0525. Epub 2020 Nov 6. PMID: 33158997; PMCID: PMC7867632. 2. Atanasova VS, Pourreyron C, Farshchian M, Lawler M, Brown CA 4th, Watt SA, Wright S, Warkala M, Guttmann-Gruber C, Hofbauer JP, Fuentes I, Prisco M, Rashidghamat E, Has C, Salas-Alanis JC, Palisson F, Hovnanian A, McGrath JA, Mellerio JE, Bauer JW, South AP. Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma. Clin Cancer Res. 2019 Jun 1;25(11):3384-3391. doi: 10.1158/1078-0432.CCR-18-2661. Epub 2019 Mar 7. PMID: 30846478; PMCID: PMC8185613. 3. Wang Y, Du P, Jiang D. Rigosertib inhibits MEK1-ERK pathway and alleviates lipopolysaccharide-induced sepsis. Immun Inflamm Dis. 2021 Jun 1. doi: 10.1002/iid3.458. Epub ahead of print. PMID: 34061465. 4. Baker SJ, Cosenza SC, Ramana Reddy MV, Premkumar Reddy E. Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia. Oncotarget. 2019 Mar 8;10(20):1932-1942. doi: 10.18632/oncotarget.26735. PMID: 30956775; PMCID: PMC6443005.
In vitro protocol: 1. Kowalczyk JT, Wan X, Hernandez ER, Luo R, Lyons GC, Wilson KM, Gallardo DC, Isanogle KA, Robinson CM, Mendoza A, Heske CM, Chen JQ, Luo X, Kelly AE, Difilippantinio S, Robey RW, Thomas CJ, Sackett DL, Morrison DK, Randazzo PA, Jenkins LMM, Yohe ME. Rigosertib Induces Mitotic Arrest and Apoptosis in RAS-Mutated Rhabdomyosarcoma and Neuroblastoma. Mol Cancer Ther. 2021 Feb;20(2):307-319. doi: 10.1158/1535-7163.MCT-20-0525. Epub 2020 Nov 6. PMID: 33158997; PMCID: PMC7867632. 2. Atanasova VS, Pourreyron C, Farshchian M, Lawler M, Brown CA 4th, Watt SA, Wright S, Warkala M, Guttmann-Gruber C, Hofbauer JP, Fuentes I, Prisco M, Rashidghamat E, Has C, Salas-Alanis JC, Palisson F, Hovnanian A, McGrath JA, Mellerio JE, Bauer JW, South AP. Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma. Clin Cancer Res. 2019 Jun 1;25(11):3384-3391. doi: 10.1158/1078-0432.CCR-18-2661. Epub 2019 Mar 7. PMID: 30846478; PMCID: PMC8185613.
In vivo protocol: 1. Wang Y, Du P, Jiang D. Rigosertib inhibits MEK1-ERK pathway and alleviates lipopolysaccharide-induced sepsis. Immun Inflamm Dis. 2021 Jun 1. doi: 10.1002/iid3.458. Epub ahead of print. PMID: 34061465. 2. Baker SJ, Cosenza SC, Ramana Reddy MV, Premkumar Reddy E. Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia. Oncotarget. 2019 Mar 8;10(20):1932-1942. doi: 10.18632/oncotarget.26735. PMID: 30956775; PMCID: PMC6443005.

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5: Squires MS, Cooke L, Lock V, Qi W, Lewis EJ, Thompson NT, Lyons JF, Mahadevan D. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8. doi: 10.1158/1535-7163.MCT-09-1071. Epub 2010 Mar 30. PubMed PMID: 20354122.

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