ON-01910

Information	ON-01910 (Estybon, Novonex, Rigosertib) is a non-ATP-competitive inhibitor to Polo-like kinase 1 (PLK1) with IC50 of 9 nM.
Targets	PLK1
IC50	9 nM ^[1]
In vitro	ON-01910 is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. ON-01910 also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18–260 nM. ON-01910 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, ON-01910 has little or no effect unless its concentration is greater than 5–10 µM. In HeLa cells, ON-01910 (100–250 nM) induces spindle abnormalities and apoptosis. ^[1] ON-01910 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, ON-01910 (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, ON-01910 (50 nM–0.5 µM) induces loss of viability and caspase 3/7 activation. ^[2] In a recent study, ON-01910 induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. ON-01910 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, ON-01910 (250 mg/kg) markedly inhibits tumor growth. ^[1] ON-01910 (200 mg/kg) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells. ^[2]
Clinical Trials	ON-01910 is currently under a Phase III clinical trial in refractory myelodysplastic syndrome patients with excess blasts.
Features

Information

ON-01910 (Estybon, Novonex, Rigosertib) is a non-ATP-competitive inhibitor to Polo-like kinase 1 (PLK1) with IC50 of 9 nM.

Targets

PLK1

IC50

9 nM ^[1]

In vitro

ON-01910 is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. ON-01910 also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18–260 nM. ON-01910 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, ON-01910 has little or no effect unless its concentration is greater than 5–10 µM. In HeLa cells, ON-01910 (100–250 nM) induces spindle abnormalities and apoptosis. ^[1] ON-01910 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, ON-01910 (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, ON-01910 (50 nM–0.5 µM) induces loss of viability and caspase 3/7 activation. ^[2] In a recent study, ON-01910 induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. ON-01910 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, ON-01910 (250 mg/kg) markedly inhibits tumor growth. ^[1] ON-01910 (200 mg/kg) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells. ^[2]

Clinical Trials

ON-01910 is currently under a Phase III clinical trial in refractory myelodysplastic syndrome patients with excess blasts.

Features

In vitro enzyme assays for PLK1	Recombinant PLK1 (10 ng) is incubated with different concentrations of ON-01910 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 ℃ 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.

Cell lines:	A number of tumor cell lines, including BT20, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, HeLa, and Raji cells
Concentrations:	1 nM–10 µM, dissolved in DMSO as stock solution.
Incubation Time:	96 hours
Method:	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 ON-01910 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.

Cell lines:

A number of tumor cell lines, including BT20, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, HeLa, and Raji cells

Concentrations:

1 nM–10 µM, dissolved in DMSO as stock solution.

Incubation Time:

96 hours

Method:

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 ON-01910 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.

Animal Models:	Mouse (female athymic, NCR-nu/nu) xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells
Formulation:	Dissolved in PBS
Dosages:	250 mg/kg
Administration:	Intraperitonially

Animal Models:

Mouse (female athymic, NCR-nu/nu) xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells

Formulation:

Dissolved in PBS

Dosages:

250 mg/kg

Administration:

Intraperitonially

Molecular Weight (WM):	473.47
Formula:	C₂₁H₂₄NNaO₈S
CAS No.:	1225497-78-8
Synonyms:	N/A

Molecular Weight (WM):

473.47

Formula:

C₂₁H₂₄NNaO₈S

CAS No.:

1225497-78-8

Synonyms:

N/A

Dissolve in (25°C):	DMSO ≥95mg/mL
	Water ≥95mg/mL
	Ethanol <1mg/mL
Storage:	2 years-20°CPowder
	1 week-4°Cin DMSO
	1 month-80°in DMSO

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Biological Activity

Protocol (Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[2]

Animal Study:^[1]

References

Chemical Information

Quality Control & MSDS

Research Area

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