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| 25mg |
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Purity: ≥98%
Rigosertib (formerly also known as ON-01910) is a novel, potent and non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It exhibits no activity toward Plk3 and a 30-fold increase in selectivity against Plk2. It may be possible to treat cancer with rigosertib. Polo-like kinase1 (Plk1) is inhibited by rigosertib, which causes reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells and selective G2/M arrest followed by apoptosis in a variety of tumor cells. When used in conjunction with other chemotherapeutic agents, this agent may show synergistic antitumor activity.
| Targets |
PLK1 (IC50 = 9 nM); PLK2 (IC50 = 260 nM); PDGFR (IC50 = 18 nM); Src (IC50 = 155 nM); BCR-ABL (IC50 = 32 nM); Cdk1 (IC50 = 260 nM); Flt1 (IC50 = 42 nM); Fyn (IC50 = 182 nM)
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| ln Vitro |
Rigosertib, which has an IC50 of 9 nM, is a non-ATP-competitive inhibitor of PLK1. Moreover, rigosertib shows inhibition with an IC50 of 18-260 nM against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1. 94 distinct tumor cell lines, including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells, exhibit cell killing activity in response to rigosertib, with an IC50 of 50–250 nM. Rigosertib, however, has little to no effect in normal cells, such as HFL, PrEC, HMEC, and HUVEC, unless the concentration is higher than 5–10 μM. Rigosertib (100-250 nM) causes spindle abnormalities and apoptosis in HeLa cells.[1] With an IC50 of 50-100 nM, rigorsertib also inhibits a number of multidrug-resistant tumor cell lines, such as MES-SA, MES-SA/DX5a, CEM, and CEM/C2a. Rigosertib (0.25–5 μM) causes an accumulation of cells with subG1 DNA content, initiates apoptotic pathways, and inhibits cell cycle progression in G2/M phase in DU145 cells. Rigosertib (50 nM-0.5 μM) causes caspase 3/7 activation and viability loss in A549 cells.[2] According to a recent study, rigosertib causes CLL (chronic lymphocytic leukemia) cells to undergo apoptosis without harming healthy B-cells or T-cells. Additionally, rigorsertib inhibits the migration of leukemic cells induced by SDF-1 and nullifies the pro-survival effect of follicular dendritic cells on CLL cells.[3]
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| ln Vivo |
Rigosertib (250 mg/kg) significantly inhibits tumor growth in mouse xenograft models of MCF-7, MIA-PaCa, and Bel-7402 cells.[1] A mouse xengraft model of BT20 cells demonstrates the inhibitory effect of rigosertib (200 mg/kg) on tumor growth.[2]
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| Enzyme Assay |
For 30 minutes at room temperature, recombinant PLK1 (10 ng) is incubated with varying concentrations of rigosertib in a 15 µL reaction mixture (50 mM HEPES, 10 mM MgCl2, 1 mM EDTA, 2 mM Dithiothreitol, 0.01% NP-40 [pH 7.5]). 20 µL (15 µL enzyme + inhibitor, 2 µL 1 mM ATP), 2 µL of γ32P-ATP (40 μCi), and 1 µL of recombinant Cdc25C (100 ng) or casein (1 μg) substrates are used in kinase reactions, which are carried out for 20 min at 30 °C. Boiling in 20 µL of 2× Laemmli buffer for 2 minutes ends the reaction. 18% SDS-PAGE is used to separate phosphorylated substrates. After drying, the gels are exposed to X-ray film for three to ten minutes.
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| Cell Assay |
One day later, different concentrations of Rigosertib are added to six-well dishes containing 1×105 cells/mL/well of tumor cells that have been plated. After treatment for 96 hours, cell counts are obtained from duplicate wells. By using trypan blue exclusion, the total number of viable cells is found.
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| Animal Protocol |
Bel-7402 tumor models: subcutaneous injection of 1 × 107 Bel-7402 tumor cells is given to twenty female athymic (NCR-nu/nu) nude mice. Ten to fourteen days later, when the tumor volumes reach 200–250 mm, the mice are divided into four groups, each of which has tumors of the same volume. Alternatively, NSC 266046 (100 mg/kg) and rigosertib (ON01910, 250 mg/kg) can be given intraperitonially on different days. Using traceable digital vernier calipers, tumor measurements are performed twice a week. During every measurement, body weight is calculated. Signs of toxicity in the animals are monitored.
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| References |
| Molecular Formula |
C₂₁H₂₅NO₈S
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|---|---|
| Molecular Weight |
451.49
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| Exact Mass |
451.13
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| Elemental Analysis |
C, 55.87; H, 5.58; N, 3.10; O, 28.35; S, 7.10
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| CAS # |
592542-59-1
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| Related CAS # |
Rigosertib sodium;592542-60-4;(E/Z)-Rigosertib sodium;1225497-78-8
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| Appearance |
Solid powder
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| SMILES |
COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
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| InChi Key |
OWBFCJROIKNMGD-BQYQJAHWSA-N
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| InChi Code |
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+
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| Chemical Name |
2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid
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| Synonyms |
ON-01910; ON01910; ON 01910; brand name: Estybon
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.54 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Saline: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2149 mL | 11.0744 mL | 22.1489 mL | |
| 5 mM | 0.4430 mL | 2.2149 mL | 4.4298 mL | |
| 10 mM | 0.2215 mL | 1.1074 mL | 2.2149 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04177498 | Recruiting | Drug: Rigosertib Sodium Other: Quality-of-Life Assessment |
Recessive Dystrophic Epidermolysis Bullosa |
Thomas Jefferson University | August 24, 2021 | Early Phase 1 |
| NCT04263090 | Completed | Drug: Rigosertib Drug: Nivolumab |
Stage IV Adenocarcinoma |
Icahn School of Medicine at Mount Sinai |
June 29, 2020 | Phase 1 Phase 2 |
| NCT03786237 | Recruiting | Drug: Rigosertib Oral Capsules / Rigosertib Intravenous |
Epidermolysis Bullosa Dystrophica Squamous Cell Carcinoma |
Prof. Johann Bauer | April 12, 2021 | Phase 1 Phase 2 |
| NCT05764395 | Recruiting | Drug: Rigosertib Procedure: Biopsy |
Metastatic Melanoma Refractory Melanoma |
Vanderbilt-Ingram Cancer Center | May 9, 2023 | Phase 2 |
| NCT02030639 | Completed | Drug: rigosertib | Healthy | Onconova Therapeutics, Inc. | January 2014 | Phase 1 |
28(ON 01910.Na) selectively induces mitotic G2/M arrest and apoptosis in cancer cells.J Med Chem.2011 Sep 22;54(18):6254-76. |
 DU145 and HFL-1 (normal human fibroblasts) cells were treated with increasing concentrations of28or DMSO (Vehicle) for 48 h.J Med Chem.2011 Sep 22;54(18):6254-76. |
Cellular viability together with the activity of caspases 3/7 were assayed concomitantly in A549 cells treated with28for 24 h (n=3).J Med Chem.2011 Sep 22;54(18):6254-76. |
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