Name: Rigosertib Sodium (ON-01910)
Brand: Selleck Chemicals
SKU: S1362
Rating: 5 (37 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.52%

99.52

Gerelateerde doelwitten	CDK HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase
Overige PLK Inhibitoren	Volasertib (BI6727) BI 2536 GSK461364 Onvansertib (NMS-1286937, NMS-P937) CFI-400945 HMN-214 Ro3280 SBE 13 HCl MLN0905 Centrinone (LCR-263)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
T47D	Cytotoxicity assay		72 hrs	Cytotoxicity against human T47D cells after 72 hrs by MTT assay, GI50 = 0.01 μM.	21463944
MDA468	Cytotoxicity assay		72 hrs	Cytotoxicity against human MDA468 cells after 72 hrs by MTT assay, GI50 = 0.02 μM.	21463944
MCF7	Cytotoxicity assay		72 hrs	Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, GI50 = 0.05 μM.	21463944
HCT116	Cytotoxicity assay		72 hrs	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, GI50 = 0.05 μM.	21463944
MDA468	Cytotoxicity assay		48 hrs	Cytotoxicity against human MDA468 cells after 48 hrs by MTT assay, GI50 = 0.302 μM.	21463944
MDA468	Cytotoxicity assay		24 hrs	Cytotoxicity against human MDA468 cells after 24 hrs by MTT assay, GI50 = 0.601 μM.	21463944
MRC5	Cytotoxicity assay		72 hrs	Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay, GI50 = 0.71 μM.	21463944
MCF7	Function assay	1 uM		Metabolic stability of the compound in human MCF7 cells at 1 uM	21463944
MRC5	Function assay	1 uM		Metabolic stability of the compound in human MRC5 cells at 1 uM	21463944
K562	Cytotoxicity assay		96 hrs	Cytotoxicity against human K562 cells after 96 hrs by trypan blue exclusion assay, IC50 = 0.0075 μM.	21812421
DU145	Cytotoxicity assay		96 hrs	Cytotoxicity against human DU145 cells after 96 hrs by trypan blue exclusion assay, IC50 = 0.075 μM.	21812421
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
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
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
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
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Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	473.47	Formule	C₂₁H₂₄NNaO₈S	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	1225497-78-8	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	COC1=C(C=C(C=C1)CS(=O)(=O)C=CC2=C(C=C(C=C2OC)OC)OC)NCC(=O)[O-].[Na+]

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 94 mg/mL (198.53 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : 94 mg/mL

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	water Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	95.000mg/ml (200.65mM)	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.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	PLK1 (Cell-free assay) 9 nM PDGFR (Cell-free assay) 18 nM Bcr-Abl (Cell-free assay) 32 nM Flt1 (Cell-free assay) 42 nM Src (Cell-free assay) 155 nM Fyn (Cell-fre assay) 182 nM CDK1 (Cell-free assay) 260 nM PLK2 (Cell-free assay) 260 nM
In vitro	Rigosertib (ON-01910) is a non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. It also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18-260 nM. This compound 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, it 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. It 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, this compound (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, it (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. It also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells.
Kinase Assay	In vitro enzymassays voor PLK1
Kinase Assay	Recombinant PLK1 (10 ng) wordt geïncubeerd met verschillende concentraties Rigosertib Sodium (ON-01910) in een reactiemengsel van 15 µL (50 mM HEPES, 10 mM MgCl₂, 1 mM EDTA, 2 mM Dithiothreitol, 0.01% NP-40 [pH 7.5]) gedurende 30 min bij kamertemperatuur. Kinasereacties worden uitgevoerd gedurende 20 min bij 30 °C in een volume van 20 µL (15 µL enzym + deze verbinding, 2 µL 1 mM ATP), 2 µL γ³²P-ATP (40 μCi) en 1 µL recombinante Cdc25C (100 ng) of caseïne (1 μg) substraten. Reacties worden beëindigd door 2 min te koken in 20 µL 2× Laemmli-buffer. Gefosforyleerde substraten worden gescheiden door middel van 18% SDS-PAGE. De gels worden gedroogd en gedurende 3-10 min blootgesteld aan röntgenfilm.
In vivo	In mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells, Rigosertib (ON-01910) (250 mg/kg) markedly inhibits tumor growth. This compound (200 mg/kg) also shows inhibition on tumor growth in a mouse xenograft model of BT20 cells.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/15766665/ [2] https://pubmed.ncbi.nlm.nih.gov/21812421/ [3] https://pubmed.ncbi.nlm.nih.gov/22351695/

Toepassingen (Applications)

Methoden	Biomarkers	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	Cell viability GI50	27764820

Informatie klinische proef (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
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

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C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Rigosertib Sodium (ON-01910) PLK1-remmer

Moleculair gewicht: 473.47

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Rigosertib Sodium (ON-01910) PLK1-remmer

Moleculair gewicht: 473.47

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)