Rigosertib sodium (ON-01910 sodium) is a multi-kinase inhibitor and a selective anti-cancer agent, which induces apoptosis by inhibition the PI3K/Akt pathway, promotes the phosphorylation of histone H2AX and induces G2/M arrest in cell cycle^[1][2]. Rigosertib sodium is a selective and non-ATP-competitive inhibitor of PLK1 with an IC₅₀ of 9 nM^[3].

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Rigosertib (250 mg/kg, i.p.) markedly inhibits tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells^[3]. Rigosertib (200 mg/kg, i.p.) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

473.47

C₂₁H₂₄NNaO₈S

592542-60-4

瑞格色替钠

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

DMSO : 150 mg/mL (316.81 mM; Need ultrasonic)

H₂O : ≥ 52 mg/mL (109.83 mM)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： PBS

  Solubility: 50 mg/mL (105.60 mM); Clear solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 5.25 mg/mL (11.09 mM); Clear solution

  此方案可获得 ≥ 5.25 mg/mL (11.09 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 52.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 5.25 mg/mL (11.09 mM); Clear solution

  此方案可获得 ≥ 5.25 mg/mL (11.09 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 52.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 5.25 mg/mL (11.09 mM); Clear solution

  此方案可获得 ≥ 5.25 mg/mL (11.09 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 52.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• 5.

  请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

  Solubility: ≥ 2.5 mg/mL (5.28 mM); Suspended solution
• 6.

  请依序添加每种溶剂： 5% DMSO    95% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.28 mM); Clear solution

• [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

Tumor cells are plated into six-well dishes at a density of 1×10⁵ cells/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 exclusion.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Bel-7402 tumor models: twenty female athymic (NCR-nu/nu) nude mice are injected with 1 × 10⁷ Bel-7402 tumor cells subcutaneously, and 10-14 days later, when the tumor volumes reach 200-250 mm, the mice are divided into four groups such that each group harbors tumors of the same volume. Rigosertib (ON01910, 250 mg/kg) dissolved in PBS is administered alone or in combination with NSC 266046 (100 mg/kg) intraperitonially on alternate days. Tumor measurements are done two times/week using traceable digital vernier calipers. Body weight is determined during each measurement. The animals are observed for signs of toxicity^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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