Size | Price | Stock | Qty |
---|---|---|---|
1mg |
|
||
5mg |
|
||
10mg |
|
||
50mg |
|
||
100mg |
|
||
Other Sizes |
|
Targets |
PLK1 9 nM (IC50) PLK2 260 nM (IC50) PDGFR 18 nM (IC50) Src 155 nM (IC50) BCR-ABL 32 nM (IC50) Cdk1 260 nM (IC50) Flt1 42 nM (IC50) Fyn 182 nM (IC50)
|
---|---|
ln Vitro |
Rigosertib has an IC50 of 9 nM and inhibits PLK1 in a non-ATP-competitive manner. Additionally, PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1 are inhibited by rigosertib, with an IC50 of 18–260 nM. 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, until the concentration is higher than 5–10 μM. Rigosertib (100-250 nM) causes spindle aberrations and apoptosis in HeLa cells[3]. Moreover, MES-SA, MES-SA/DX5a, CEM, and CEM/C2a are among the multidrug-resistant tumor cell lines that rigosertib suppresses with an IC50 of 50–100 nM. In DU145 cells, rigosertib (0.25–5 μM) inhibits the G2/M phase of the cell cycle, causes a build-up of cells with DNA content in the subG1 region, and triggers apoptotic pathways. In A549 cells, rigosertib (50 nM-0.5 μM) causes caspase 3/7 activation and viability loss[4]. Inducing apoptosis in chronic lymphocytic leukemia (CLL) cells, rigosertib sodium (2 μM) does not cause harm to T-cells or healthy B-cells. Additionally, the pro-survival effect of follicular dendritic cells on CLL cells is eliminated by rigosertib sodium (2 μM), which also lessens the migration of leukemic cells produced by SDF-1[5].
|
ln Vivo |
Tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells is significantly inhibited by rigosertib (250 mg/kg, ip)[3]. BT20 cell tumor growth is inhibited in a mouse xengraft model by rigosertib (200 mg/kg, ip)[4].
|
References |
[1]. Xu F, et al. Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signalingtransduction pathways in high-grade myelodysplastic syndrome. Sci Rep. 2014 Dec 4;4:7310.
[2]. Hyoda T, et al. Rigosertib induces cell death of a myelodysplastic syndrome-derived cell line by DNA damage-induced G2/M arrest. Cancer Sci. 2015 Mar;106(3):287-93. [3]. Gumireddy K, et al. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005 Mar;7(3):275-86. [4]. Reddy MV, et al. Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): synthesis, structure-activity relationship, and biological activity. J Med Chem. [5]. Chapman CM, et al. ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91 |
Molecular Formula |
C21H24NNAO8S
|
---|---|
Molecular Weight |
473.47
|
CAS # |
592542-60-4
|
Related CAS # |
Rigosertib;592542-59-1;(E/Z)-Rigosertib sodium;1225497-78-8
|
SMILES |
COC1=CC=C(C=C1NCC([O-])=O)CS(/C=C/C2=C(C=C(C=C2OC)OC)OC)(=O)=O.[Na+]
|
Solubility (In Vitro) |
DMSO : 150 mg/mL (316.81 mM)
H2O : ≥ 52 mg/mL (109.83 mM) |
---|---|
Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.25 mg/mL (11.09 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 52.5 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: ≥ 5.25 mg/mL (11.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 52.5 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: ≥ 5.25 mg/mL (11.09 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: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 6: 50 mg/mL (105.60 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.1121 mL | 10.5603 mL | 21.1207 mL | |
5 mM | 0.4224 mL | 2.1121 mL | 4.2241 mL | |
10 mM | 0.2112 mL | 1.0560 mL | 2.1121 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.