ON-01910

ON-01910 is a synthetic benzyl styryl sulfone analogue with potential antineoplastic activity. Polo-like kinase 1 inhibitor ON 01910.Na inhibits polo-like kinase1 (Plk1), inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. This agent may exhibit synergistic antitumor activity in combination with other chemotherapeutic agents. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner. Note: this product is supplied as sodium salt.

Product information

CAS Number: 592542-60-4

Molecular Weight: 473.47

Formula: C21H24NNaO8S

Synonym:

Rigosertib sodium

Estybon

ON-01910

Related CAS Number:

592542-59-1 (Rigosertib free acid)

1225497-78-8 (Rigosertib Sodium(EZ))

Chemical Name: sodium (E)-2-((2-methoxy-5-(((2, 4, 6-trimethoxystyryl)sulfonyl)methyl)phenyl)amino)acetate

Smiles: [Na+].COC1C=C(OC)C(/C=C/S(=O)(=O)CC2C=C(NCC([O-])=O)C(=CC=2)OC)=C(C=1)OC

InChiKey: VLQLUZFVFXYXQE-USRGLUTNSA-M

InChi: InChI=1S/C21H25NO8S.Na/c1-27-15-10-19(29-3)16(20(11-15)30-4)7-8-31(25,26)13-14-5-6-18(28-2)17(9-14)22-12-21(23)24;/h5-11,22H,12-13H2,1-4H3,(H,23,24);/q;+1/p-1/b8-7+;

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 95 mg/mL(200.64 mM). Water: 95 mg/mL(200.64 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. 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. 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.

In Vivo:

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

References:

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

Products are for research use only. Not for human use.