Rigosertib (ON-01910)

製品コード：S1362 純度：99.28%

Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Rigosertib inhibits PI3K/Akt pathway and activates oxidative stress signals. Rigosertib induces apoptosis in various cancer cells. Phase 3.

CAS No. 1225497-78-8

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 25500	国内在庫あり
10mg	JPY 48000	国内在庫あり
50mg	JPY 118500	国内在庫あり
1g	JPY 598500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（34）

製品安全説明書

現在のバッチを見る：純度： 99.28%

99.28

Rigosertib (ON-01910)関連製品

関連ターゲット	PLK1 PLK2 PLK3 PLK4	もっと見る
関連製品	BI 2536 Volasertib GSK461364 Onvansertib (NMS-P937) SBE 13 HCl Ro3280 CFI-400945 HMN-214 MLN0905 Poloxin	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

PLKシグナル伝達経路

PLK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
A2780	Function assay	0.25 uM	24 hrs	Reduction in CDC25C level in human A2780 cells at 0.25 uM after 24 hrs by Western blot analysis	24471873
A2780	Apoptosis assay	0.25 uM	24 hrs	Induction of apoptosis in human A2780 cells assessed as caspase-3/7 activation at 0.25 uM after 24 hrs by using Apo-ONE homogeneous caspase-3/7 kit	24471873
A2780	Function assay	0.25 uM	24 hrs	Reduction in Mcl1 level in human A2780 cells at 0.25 uM after 24 hrs by Western blot analysis	24471873
MRC5	Function assay	1 uM		Metabolic stability of the compound in human MRC5 cells at 1 uM	21463944
MCF7	Function assay	1 uM		Metabolic stability of the compound in human MCF7 cells at 1 uM	21463944
LNCAP	Antiproliferative assay		72 hrs	Antiproliferative activity against AR positive human LNCAP cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.025 μM.	24471873
HeLa	Antiproliferative assay		72 hrs	Antiproliferative activity against human HeLa cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.012 μM.	24471873
DU145	Cytotoxicity assay		96 hrs	Cytotoxicity against human DU145 cells after 96 hrs by trypan blue exclusion assay, IC50 = 0.075 μM.	21812421
K562	Cytotoxicity assay		96 hrs	Cytotoxicity against human K562 cells after 96 hrs by trypan blue exclusion assay, IC50 = 0.0075 μM.	21812421
MRC5	Cytotoxicity assay		72 hrs	Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay, GI50 = 0.71 μM.	21463944
MDA468	Cytotoxicity assay		24 hrs	Cytotoxicity against human MDA468 cells after 24 hrs by MTT assay, GI50 = 0.601 μM.	21463944
MDA468	Cytotoxicity assay		48 hrs	Cytotoxicity against human MDA468 cells after 48 hrs by MTT assay, GI50 = 0.302 μM.	21463944
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, GI50 = 0.05 μM.	21463944
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, GI50 = 0.05 μM.	21463944
MDA468	Cytotoxicity assay		72 hrs	Cytotoxicity against human MDA468 cells after 72 hrs by MTT assay, GI50 = 0.02 μM.	21463944
T47D	Cytotoxicity assay		72 hrs	Cytotoxicity against human T47D cells after 72 hrs by MTT assay, GI50 = 0.01 μM.	21463944
PANC1	Antiproliferative assay		72 hrs	Antiproliferative activity against human PANC1 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.039 μM.	24471873
MCF7	Antiproliferative assay		72 hrs	Antiproliferative activity against ER positive human MCF7 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.05 μM.	24471873
MCF7	Antiproliferative assay		72 hrs	Antiproliferative activity against human MCF7 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.05 μM.	24471873
MDA-MB-231	Antiproliferative assay		72 hrs	Antiproliferative activity against ER negative human MDA-MB-231 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.057 μM.	24471873
A2780	Antiproliferative assay		72 hrs	Antiproliferative activity against human A2780 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.062 μM.	24471873
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.07 μM.	24471873
DU145	Antiproliferative assay		72 hrs	Antiproliferative activity against AR negative human DU145 cells assessed as cell growth inhibition after 72 hrs by MTT assay, GI50 = 0.075 μM.	24471873
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Targets

PLK1 ^[1] (Cell-free assay)	PDGFR ^[1] (Cell-free assay)	Bcr-Abl ^[1] (Cell-free assay)	Flt1 ^[1] (Cell-free assay)	Src ^[1] (Cell-free assay)	もっとクリックする
9 nM	18 nM	32 nM	42 nM	155 nM	もっとクリックする

In Vitro
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]
Kinase Assay	In vitro enzyme assays for PLK1
Kinase Assay	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.
細胞実験	細胞株	A number of tumor cell lines, including BT20, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, HeLa, and Raji cells
	濃度	1 nM - 10 μM, dissolved in DMSO as stock solution.
	反応時間	96 hours
	実験の流れ	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
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pAbl / Abl / PCrk-L / Crk-L / Cleaved caspase3 / Cleaved PARP / pHistone H2A.X		26008977
	Immunofluorescence	p-ATF / COX IV		27764820
	Growth inhibition assay	GI50 Cell viability		29108241

In Vivo
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]
動物実験	動物モデル	Mouse (female athymic, NCR-nu/nu) xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells
	投与量	250 mg/kg
	投与経路	Intraperitonially

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT04177498	Recruiting	Recessive Dystrophic Epidermolysis Bullosa	Thomas Jefferson University\|Traws Pharma Inc.	August 24 2021	Early Phase 1
NCT02075034	Withdrawn	Myelodysplastic Syndrome	Traws Pharma Inc.	May 2014	Phase 1
NCT02030639	Completed	Healthy	Traws Pharma Inc.	January 2014	Phase 1
NCT01928537	Completed	Myelodysplastic Syndromes\|Refractory Anemia With Excess Blasts\|Chronic Myelomonocytic Leukemia\|Cytopenia	Traws Pharma Inc.	August 2013	Phase 3
NCT01807546	Completed	Head and Neck Squamous Cell Carcinoma\|Anal Squamous Cell Carcinoma\|Lung Squamous Cell Carcinoma\|Cervical Squamous Cell Carcinoma\|Esophageal Squamous Cell Carcinoma\|Skin Squamous Cell Carcinoma\|Penile Squamous Cell Carcinoma	Traws Pharma Inc.	March 2013	Phase 2
NCT01168011	Completed	Solid Tumor	Traws Pharma Inc.	July 2010	Phase 1

参考
[1] Gumireddy K, et al. Cancer Cell, 2005, 7(3), 275-286. [2] Reddy MV, et al. J Med Chem, 2011, 54(18), 6254-6276. [3] Chapman CM, et al. Clin Cancer Res, 2012 18(7), 1979-1991.

参考

化学情報

分子量	473.47	化学式	C₂₁H₂₄NNaO₈S
CAS No.	1225497-78-8	SDF	Download Rigosertib (ON-01910) SDFをダウンロードする
Smiles	COC1=C(C=C(C=C1)CS(=O)(=O)C=CC2=C(C=C(C=C2OC)OC)OC)NCC(=O)[O-].[Na+]
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 95 mg/mL ( (200.64 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : 95 mg/mL

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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C4=C3/X	C4:	LOG(C4):
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