Rigosertib (ON-01910)

製品コードS1362 バッチS136208

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H24NNaO8S
分子量 473.47 CAS No. 1225497-78-8
Solubility (25°C)* 体外 DMSO 95 mg/mL (200.64 mM)
Water 95 mg/mL (200.64 mM)
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
water
95.0mg/ml Taking the 1 mL working solution as an example, add 95 mg of this product to 1 ml of ddH2O, mix evenly to make it clear, The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 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
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
投薬量 250 mg/kg
投与方法 Intraperitonially

カスタマーフィードバック

Data from [Data independently produced by PLoS One, 2013, 8(11), e79863]

Data independently produced by Dr Antonino Maria Sparta, PhD University of Bologna.,

, , Dr. Antonino Maria Sparta, PhD University of Bologna

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] PubMed: 38453961
Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity [ Cancer Cell, 2022, 40(7):754-767.e6] PubMed: 35820397
IGF2BP3 is an essential N6-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells [ Mater Today Bio, 2022, 17:100503] PubMed: 36457846
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] PubMed: 35326726
In vitro human cell-based aneugen molecular mechanism assay [ Environ Mol Mutagen, 2022, 63(3):151-161] PubMed: 35426156
Elevated FBXO45 promotes liver tumorigenesis through enhancing IGF2BP1 ubiquitination and subsequent PLK1 upregulation [ Elife, 2021, 10e70715] PubMed: 34779401
Efficacy of rigosertib, a small molecular RAS signaling disrupter for the treatment of KRAS-mutant colorectal cancer [ Cancer Biol Med, 2021, j.issn.2095-3941.2020.0532] PubMed: 34347396
Rigosertib inhibits MEK1-ERK pathway and alleviates lipopolysaccharide-induced sepsis [ Immun Inflamm Dis, 2021, 10.1002/iid3.458] PubMed: 34061465
Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent [ Mol Cell, 2020, 79(1):191-198.e3] PubMed: 32619469
Rigosertib-Activated JNK1/2 Eliminate Tumor Cells Through p66Shc Activation [ Biology (Basel), 2020, 15;9(5):E99] PubMed: 32429320

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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