Antibodies
Rigosertib (ON-01910)
- 貨號 Cat. No.
- S1362
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Rigosertib (ON-01910)
Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Phase 3.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Phase 3. | |||||
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| Targets | PLK1 | |||||
| IC50 | 9 nM [1] | |||||
| In vitro | Rigosertib is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. Rigosertib also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18-260 nM. Rigosertib shows cell killing activity against 94 different tumor cell lines with IC50 of 50-250 nM, including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. While in normal cells, such as HFL, PrEC, HMEC, and HUVEC, Rigosertib has little or no effect unless its concentration is greater than 5-10 μM. In HeLa cells, Rigosertib (100-250 nM) induces spindle abnormalities and apoptosis. [1] Rigosertib also inhibits several multidrug resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a, with IC50 of 50-100 nM. In DU145 cells, Rigosertib (0.25-5 μM) blocks cell cycle progression in G2/M phase, results in an accumulation of cells containing subG1 content of DNA, and activates apoptotic pathways. In A549 cells, Rigosertib (50 nM-0.5 μM) induces loss of viability and caspase 3/7 activation. [2] In a recent study, Rigosertib induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells. [3] | |||||
| In vivo | In mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells, Rigosertib (250 mg/kg) markedly inhibits tumor growth. [1] Rigosertib (200 mg/kg) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells. [2] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| In vitro enzyme assays for PLK1 | Recombinant PLK1 (10 ng) is incubated with different 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]) for 30 min at room temperature. Kinase reactions are performed for 20 min at 30 °C in a volume of 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. Reactions are terminated by boiling for 2 min in 20 µL of 2× Laemmli buffer. Phosphorylated substrates are separated by 18% SDS-PAGE. The gels are dried and exposed to X-ray film for 3-10 min. |
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Cell Assay: [2]
| Cell lines | A number of tumor cell lines, including BT20, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, HeLa, and Raji cells |
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| Concentrations | 1 nM - 10 μM, dissolved in DMSO as stock solution. |
| Incubation Time | 96 hours |
| Method | Cells are grown in either DMEM or RPMI supplemented with 10% fetal bovine serum and 1 unit/mL penicillin-streptomycin solution. Tumor cells are plated into six-well dishes at a density of 1 × 105cells/mL/well, and Rigosertib is added 24 hours later at various concentrations. Cell counts are determined from duplicate wells after 96-hour of treatment. The total number of viable cells is determined by trypan blue exclusio |
Animal Study: [1]
| Animal Models | Mouse (female athymic, NCR-nu/nu) xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells |
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| Dosages | 250 mg/kg |
| Administration | Intraperitonially |
| Solubility | Saline, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01241500 | Active, not recruiting | Myelodysplastic Syndromes|MDS|RAEB|Chronic Myelomonocytic Leukemia | Onconova Therapeutics, Inc.|The Leukemia and Lymphoma Society | 2010-11 | Phase 3 |
| NCT01360853 | Recruiting | Metastatic Pancreatic Adenocarcinoma | Onconova Therapeutics, Inc.|Academic Oncology Gastrointestinal Cancer Consortium (AGICC) | 2011-05 | Phase 3 |
| NCT01584531 | Recruiting | Myelodysplastic Syndrome|MDS|Trisomy 8 | Onconova Therapeutics, Inc. | 2012-05 | Phase 2 |
| NCT01700335 | Recruiting | Myelodysplastic Syndrome | SymBio Pharmaceuticals | 2012-06 | Phase 1 |
| NCT01807546 | Recruiting | Head and Neck Squamous Cell Carcinoma|Anal Squamous Cell Carcinoma|Lung Squamous Cell Carcinoma|Cervical Squamous Cell Carcinoma|Esophageal Squamous Cell Carcinoma | Onconova Therapeutics, Inc. | 2013-03 | Phase 2 |
Chemical Information
Download Rigosertib (ON-01910) SDF
| Molecular Weight (MW) | 473.47 |
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| Formula | C21H24NNaO8S |
| CAS No. | 1225497-78-8 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 95 mg/mL (200 mM) |
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| Water | 95 mg/mL (200 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | Saline, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.47347 | 4.7347 | 9.4694 | 14.2041 |
Customer Reviews (2)
 Click to enlarge | Rating | |
| Source | Rigosertib (ON-01910) purchased from Selleck | |
| Method | MTT Assay | |
| Cell Lines | leukemia cell lines | |
| Concentrations | 0.001-1 μM | |
| Incubation Time | 48 h | |
| Results | ON01910 demonstrated a good capacity to inhibit leukemia cell growth in a concentration dependent manner. |
Product Citations (3)
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res 2013;73(20):6310-22]
MELK-dependent FOXM1 Phosphorylation is Essential for Proliferation of Glioma Stem Cells. [Joshi K, et al. Stem Cells 2013;31(6):1051-63]
Ran GTPase-Activating Protein 1 Is a Therapeutic Target in Diffuse Large B-Cell Lymphoma. [Chang KC, et al. PLoS One 2013;8(11):e79863]
