Rigosertib sodiumPlk1 inhibitor CAS# 592542-60-4 |
- Ro3280
Catalog No.:BCC3962
CAS No.:1062243-51-9
- MLN0905
Catalog No.:BCC3961
CAS No.:1228960-69-7
- Rigosertib
Catalog No.:BCC4296
CAS No.:592542-59-1
- Rigosertib sodium
Catalog No.:BCC4067
CAS No.:592542-60-4
- GW843682X
Catalog No.:BCC1614
CAS No.:660868-91-7
- GSK461364
Catalog No.:BCC3788
CAS No.:929095-18-1
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 592542-60-4 | SDF | Download SDF |
PubChem ID | 23696523 | Appearance | Powder |
Formula | C21H24NNaO8S | M.Wt | 473.47 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | 1225497-78-8;Rigosertib sodium; Novonex; Estybon | ||
Solubility | DMSO : 150 mg/mL (316.81 mM; Need ultrasonic) H2O : ≥ 52 mg/mL (109.83 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | sodium;2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetate | ||
SMILES | COC1=C(C=C(C=C1)CS(=O)(=O)C=CC2=C(C=C(C=C2OC)OC)OC)NCC(=O)[O-].[Na+] | ||
Standard InChIKey | VLQLUZFVFXYXQE-USRGLUTNSA-M | ||
Standard InChI | 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+; | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Rigosertib is a non-ATP-competitive small-molecule inhibitor of Plk1 with IC50 value of 9 nM.Rigosertib (sodium) is a non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM, and shows 30-fold greater selectivity against PLK2.In Vitro:Rigosertib is non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM. Rigosertib also exhibits inhibition of 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]. Rigosertib sodium (2 μM) induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib sodium (2 μM) 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:Rigosertib (250 mg/kg, i.p.) markedly inhibits tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells[1]. Rigosertib (200 mg/kg, i.p.) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells[2]. References: |
Rigosertib sodium Dilution Calculator
Rigosertib sodium Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.1121 mL | 10.5603 mL | 21.1207 mL | 42.2413 mL | 52.8017 mL |
5 mM | 0.4224 mL | 2.1121 mL | 4.2241 mL | 8.4483 mL | 10.5603 mL |
10 mM | 0.2112 mL | 1.056 mL | 2.1121 mL | 4.2241 mL | 5.2802 mL |
50 mM | 0.0422 mL | 0.2112 mL | 0.4224 mL | 0.8448 mL | 1.056 mL |
100 mM | 0.0211 mL | 0.1056 mL | 0.2112 mL | 0.4224 mL | 0.528 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Rigosertib sodium (ON-01910 sodium) 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.Rigosertib has been used in trials studying the treatment and basic science of MDS, RAEB, Cancer, Hepatoma, and Neoplasms, among others
Rigosertib (ON-01910,Estybon) is a potent, specific PLK1 inhibitor with IC50 value of 9nM. Rigosertib strongly inhibited the proliferation of cancer cell lines, with observed IC50?values in the nanomolar range for both HeLa (115?nM) and C33A (45?nM) cells. In contrast, rigosertib had a minimal effect on normal cell lines, BJ and Ect1/E6E7 (IC50?>?0.1?mM) [1]
HeLa and C33A cells demonstrated a complete (>95%) G2/M arrest at concentrations of rigosertib >0.5?μM, whereas at <0.2?μM no clear perturbation of the cell cycle was evident. Normal cells were less affected by rigosertib [1].
Rigosertib has been reported to be a more potent radiosensitizer than cisplatin in?vivo [1].
References:
[1] Agoni L1,?Basu I2,?Gupta S3,?Alfieri A2,?Gambino A4,?Goldberg GL5,?Reddy EP6,?Guha C7. Rigosertib is a more effective radiosensitizer than cisplatin in concurrent chemoradiation treatment of cervical carcinoma, in vitro and in vivo. Int J Radiat Oncol Biol Phys.?2014 Apr 1;88(5):1180-7.
?
- Rigosertib
Catalog No.:BCC4296
CAS No.:592542-59-1
- Chikusetsu Saponin Ib
Catalog No.:BCC8308
CAS No.:59252-87-8
- Laurocapram
Catalog No.:BCN8308
CAS No.:59227-89-3
- Erigeroside
Catalog No.:BCC8171
CAS No.:59219-76-0
- Darutoside
Catalog No.:BCN4094
CAS No.:59219-65-7
- 8(14),15-Isopimaradiene-3,18-diol
Catalog No.:BCN4093
CAS No.:59219-64-6
- beta-Dihydroplumericinic acid
Catalog No.:BCN4092
CAS No.:59204-61-4
- Sulforaphene
Catalog No.:BCN8179
CAS No.:592-95-0
- PSB 10 hydrochloride
Catalog No.:BCC7238
CAS No.:591771-91-4
- Neoisoliquiritin
Catalog No.:BCN2936
CAS No.:59122-93-9
- Misoprostol
Catalog No.:BCC5240
CAS No.:59122-46-2
- Alpha-Angelica lactone
Catalog No.:BCN5001
CAS No.:591-12-8
- Meptazinol HCl
Catalog No.:BCC4920
CAS No.:59263-76-2
- Acyclovir
Catalog No.:BCC3929
CAS No.:59277-89-3
- Decursin
Catalog No.:BCN5335
CAS No.:5928-25-6
- Sissotrin
Catalog No.:BCN4095
CAS No.:5928-26-7
- Vitexin 2''-O-p-coumarate
Catalog No.:BCN2793
CAS No.:59282-55-2
- Lindleyin
Catalog No.:BCN8450
CAS No.:59282-56-3
- Triacontanol
Catalog No.:BCC8260
CAS No.:593-50-0
- Alizapride HCl
Catalog No.:BCC4618
CAS No.:59338-87-3
- PIK-93
Catalog No.:BCC2519
CAS No.:593960-11-3
- Darutigenol
Catalog No.:BCN4096
CAS No.:5940-00-1
- Boc-HoSer(Bzl)-OH
Catalog No.:BCC3244
CAS No.:59408-74-1
- 1F-Fructofuranosylnystose
Catalog No.:BCN8287
CAS No.:59432-60-9
Determination of intestinal permeability of rigosertib (ON 01910.Na, Estybon): correlation with systemic exposure.[Pubmed:23738723]
J Pharm Pharmacol. 2013 Jul;65(7):960-9.
OBJECTIVES: Rigosertib (ON 01910.Na, Estybon) is a novel, anticancer agent undergoing phase 3 clinical trials for a lead indication against myelodysplastic syndromes (MDS). In this research, the permeability of rigosertib was evaluated using the in-situ perfused rat intestine (IPRI) model to support development of an oral formulation for rigosertib for treating cancer patients. METHODS: Experiments (n = 6 per group) were conducted using male Sprague-Dawley rats. Studies evaluated permeability across various intestinal segments and assessed the dose-linearity of absorption over the entire intestinal length. Drug concentrations in the portal and jugular vein were collected to correlate permeability parameters with presystemic and systemic exposure. KEY FINDINGS: Rigosertib permeability was highest in the jejunum, although parameter estimates indicated that rigosertib was a medium permeability compound. The compound displayed nonlinear absorption in the IPRI model, suggesting a saturable transport process. Transport inhibition studies using Caco-2 cells demonstrated that rigosertib was a P-glycoprotein (P-gp) substrate. Absolute bioavailability of rigosertib (10 and 20 mg/kg, 1-h infusion) in rats was estimated to be 10-15%. However, the fraction absorbed in humans predicted from IPRI data (52%) was consistent with published clinical data for rigosertib (35% oral bioavailability). CONCLUSIONS: The results of this research indicated that rigosertib is a promising candidate for oral delivery. Further studies are needed to evaluate the potential impact of P-gp and other intestinal transporters on the oral absorption of this promising anticancer agent.
ON 01910.Na (rigosertib) inhibits PI3K/Akt pathway and activates oxidative stress signals in head and neck cancer cell lines.[Pubmed:27764820]
Oncotarget. 2016 Nov 29;7(48):79388-79400.
Squamous cell carcinoma of the head and neck (HNSCC) is characterized by high morbidity and mortality. Treatment failure, drug resistance and chemoradiation toxicity have necessitated the development of alternative treatment strategies. Styryl benzyl sulfones, a family of novel small molecule inhibitors, are being evaluated as anti-neoplastic agents in multiple clinical trials. The activity of these compounds has been well characterized in several preclinical tumor studies, but their activity has yet to be fully examined in HNSCC. We tested ON 01910.Na (rigosertib), a styryl benzyl sulfone in late-stage development, in HNSCC preclinical models. Rigosertib induced cytotoxicity in both HPV(+) and HPV(-) HNSCC cells in a dose-dependent manner. Characterization of the underlying molecular mechanism indicated that rigosertib induced inhibition of the PI3K/Akt/mTOR pathway, induced oxidative stress resulting in increased generation of reactive oxygen species (ROS), and activated extracellular signal-regulated kinases (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Increased phosphorylation and cytoplasmic translocation of ATF-2 were also observed following rigosertib treatment. These changes in cell signaling led us to consider combining rigosertib with HNSCC standard-of-care therapies, such as cisplatin and radiation. Our study highlights the promising preclinical activity of rigosertib in HNSCC irrespective of HPV status and provides a molecular basis for rigosertib in combination with standard of care agents for HNSCC.
The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes.[Pubmed:27400247]
Expert Rev Anticancer Ther. 2016 Aug;16(8):805-10.
INTRODUCTION: Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndromes (MDS), but patients who relapse or are refractory have a poor prognosis with an estimated survival of 4-6 months. Rigosertib, a Ras mimetic that inhibits the phophoinositide 3-kinase and polo-like kinase pathways, has been tested in patients with higher-risk MDS following treatment with HMAs, where there are no approved second-line therapies. AREAS COVERED: This review will provide an overview of rigosertib, including safety and efficacy demonstrated in clinical trials. Expert commentary: There is an urgent need for new treatment options for patients who have failed or progressed on HMAs. Rigosertib is currently undergoing testing as a single agent in certain subsets of higher-risk MDS patients as well as in combination with azacitidine, where preliminary data show efficacy in patients with de novo MDS as well as HMA failures.
ON 01910.Na inhibits growth of diffuse large B-cell lymphoma by cytoplasmic sequestration of sumoylated C-MYB/TRAF6 complex.[Pubmed:27150054]
Transl Res. 2016 Sep;175:129-143.e13.
Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma, shows either no response or development of resistance to further treatment in 30% of the patients that warrants the development of novel drugs. We have reported that ON 01910.Na (rigosertib), a multikinase inhibitor, is selectively cytotoxic for DLBCL and induces more hyperphosphorylation and sumoylation of Ran GTPase-activating protein 1 (RanGAP1) in DLBCL cells than in non-neoplastic lymphoblastoid cell line. However, the exact mechanism of rigosertib-induced cell death in DLBCL remains to be clarified. Here, we analyzed the efficacy of rigosertib against DLBCL cells in vitro and in vivo and its molecular effects on tumor biology. We found for the first time that rigosertib attenuated expression of unmodified and sumoylated tumor necrosis factor receptor-associated factor 6 (TRAF6) and c-Myb and inhibited nuclear entry of sumoylated RanGAP1, TRAF6, and c-Myb that was confirmed by immunofluorescence. Moreover, co-immunoprecipitation showed that rigosertib induced sequestration of c-Myb and TRAF6 in the cytoplasm by stimulating their sumoylation through the RanGAP1*SUMO1/Ubc9 pathway. Specific knockdown of c-Myb and TRAF6 induced tumor cell apoptosis and cell cycle arrest at G1 phase. Xenograft mice bearing lymphoma cells also exhibited effective tumor regression on rigosertib treatment along with cytoplasmic expression of c-Myb and TRAF6. Nuclear expression of c-Myb in clinical cases of DLBCL correlated with a poor prognosis. Thus, suppression of c-Myb and TRAF6 activity may have therapeutic implication in DLBCL. These data support the clinical development of rigosertib in DLBCL.
Blockade of RAS-Binding Domain Interactions Inhibits RAS Signaling.[Pubmed:27150538]
Cancer Discov. 2016 Jun;6(6):573.
Rigosertib acts as a RAS mimetic, binding to the RAS-binding domain of multiple RAS effector proteins.
Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced Phospho-Regulatory Circuit.[Pubmed:27889448]
Mol Cell. 2016 Dec 1;64(5):875-887.
Ras pathway signaling plays a critical role in cell growth control and is often upregulated in human cancer. The Raf kinases selectively interact with GTP-bound Ras and are important effectors of Ras signaling, functioning as the initiating kinases in the ERK cascade. Here, we identify a route for the phospho-inhibition of Ras/Raf/MEK/ERK pathway signaling that is mediated by the stress-activated JNK cascade. We find that key Ras pathway components, the RasGEF Sos1 and the Rafs, are phosphorylated on multiple S/TP sites in response to JNK activation and that the hyperphosphorylation of these sites renders the Rafs and Sos1 unresponsive to upstream signals. This phospho-regulatory circuit is engaged by cancer therapeutics, such as rigosertib and paclitaxel/Taxol, that activate JNK through mitotic and oxidative stress as well as by physiological regulators of the JNK cascade and may function as a signaling checkpoint to suppress the Ras pathway during conditions of cellular stress.