Reagentes e instrumentos para imunologia, biologia celular e biologia molecular.

Rigosertib [592542-59-1]

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Referência HY-12037A-10mg

Tamanho : 10mg

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Description

Rigosertib (ON-01910) is a multi-kinase inhibitor and a selective anti-cancer agent, which induces apoptosis by inhibition the PI3 kinase/Akt pathway, promots the phosphorylation of histone H2AX and induces G2/M arrest in cell cycle^[1]^[2]. Rigosertib is a selective and non-ATP-competitive inhibitor of PLK1 with an IC₅₀ of 9 nM^[3].

IC₅₀ & Target^[1]

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)

Cellular Effect

Cell Line	Type	Value	Description	References
A2780	GI₅₀	0.062 μM Compound: ON01910	Antiproliferative activity against human A2780 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against human A2780 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
DU-145	GI₅₀	0.075 μM Compound: ON01910	Antiproliferative activity against AR negative human DU145 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against AR negative human DU145 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
DU-145	IC₅₀	0.075 μM Compound: 27a	Cytotoxicity against human DU145 cells after 96 hrs by trypan blue exclusion assay Cytotoxicity against human DU145 cells after 96 hrs by trypan blue exclusion assay	[PMID: 21812421]
HCT-116	GI₅₀	0.05 μM Compound: 3j	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay	[PMID: 21463944]
HCT-116	GI₅₀	0.07 μM Compound: ON01910	Antiproliferative activity against human HCT116 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against human HCT116 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
HeLa	GI₅₀	0.012 μM Compound: ON01910	Antiproliferative activity against human HeLa cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against human HeLa cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
K562	IC₅₀	0.0075 μM Compound: 27a	Cytotoxicity against human K562 cells after 96 hrs by trypan blue exclusion assay Cytotoxicity against human K562 cells after 96 hrs by trypan blue exclusion assay	[PMID: 21812421]
LNCaP	GI₅₀	0.025 μM Compound: ON01910	Antiproliferative activity against AR positive human LNCAP cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against AR positive human LNCAP cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
MCF7	GI₅₀	0.05 μM Compound: 3j	Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay	[PMID: 21463944]
MCF7	GI₅₀	0.05 μM Compound: ON01910	Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
MCF7	GI₅₀	0.05 μM Compound: ON01910	Antiproliferative activity against ER positive human MCF7 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against ER positive human MCF7 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
MDA-MB-231	GI₅₀	0.057 μM Compound: ON01910	Antiproliferative activity against ER negative human MDA-MB-231 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against ER negative human MDA-MB-231 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
MDA-MB-468	GI₅₀	0.02 μM Compound: 3j	Cytotoxicity against human MDA468 cells after 72 hrs by MTT assay Cytotoxicity against human MDA468 cells after 72 hrs by MTT assay	[PMID: 21463944]
MDA-MB-468	GI₅₀	0.302 μM Compound: 3j	Cytotoxicity against human MDA468 cells after 48 hrs by MTT assay Cytotoxicity against human MDA468 cells after 48 hrs by MTT assay	[PMID: 21463944]
MDA-MB-468	GI₅₀	0.601 μM Compound: 3j	Cytotoxicity against human MDA468 cells after 24 hrs by MTT assay Cytotoxicity against human MDA468 cells after 24 hrs by MTT assay	[PMID: 21463944]
MRC5	GI₅₀	0.71 μM Compound: 3j	Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay	[PMID: 21463944]
PANC-1	GI₅₀	0.039 μM Compound: ON01910	Antiproliferative activity against human PANC1 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against human PANC1 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]
T47D	GI₅₀	< 0.01 μM Compound: 3j	Cytotoxicity against human T47D cells after 72 hrs by MTT assay Cytotoxicity against human T47D cells after 72 hrs by MTT assay	[PMID: 21463944]
WI-38	GI₅₀	> 10 μM Compound: ON01910	Antiproliferative activity against human WI38 cells assessed as cell growth inhibition after 72 hrs by MTT assay Antiproliferative activity against human WI38 cells assessed as cell growth inhibition after 72 hrs by MTT assay	[PMID: 24471873]

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^[3]. 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^[4]. 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^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Solvant et solubilité

In Vitro:

DMSO : 75 mg/mL (166.12 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. The compound is unstable in solutions, freshly prepared is recommended.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.54 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.54 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.54 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Pureté et documentation

Purity: 99.01%

Fiche technique (280 KB) SDS (393 KB)

COA (246 KB) RP-HPLC (235 KB)

Instruction de manipulation (2659 KB)

Références

[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. [Content Brief]

[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. [Content Brief]

[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. [Content Brief]

[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. [Content Brief]

[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 [Content Brief]

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Referência HY-12037A-10mg

Contactar o distribuidor local :

Marca : MedChemExpress

Contactar o distribuidor local :

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