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

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Contrôle Qualité (Quality Control)

Lot : Pureté : 99.52%

99.52

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

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires	Type d'essai	Concentration	Temps d'incubation	Description de l'activité	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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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire	473.47	Formule	C₂₁H₂₄NNaO₈S	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	1225497-78-8	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	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+]

Solubilité (Solubility)

In vitro
Lot:

DMSO : 94 mg/mL (198.53 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : 94 mg/mL

Ethanol : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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 Validé par les laboratoires Selleck. Si vous avez besoin d'ajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre d'animaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (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.
Essai kinase	Tests enzymatiques in vitro pour PLK1
Essai kinase	La PLK1 recombinante (10 ng) est incubée avec différentes concentrations de Rigosertib (ON-01910) dans un mélange réactionnel de 15 µL (50 mM HEPES, 10 mM MgCl₂, 1 mM EDTA, 2 mM Dithiothréitol, 0,01 % NP-40 [pH 7,5]) pendant 30 min à température ambiante. Les réactions de kinase sont effectuées pendant 20 min à 30 °C dans un volume de 20 µL (15 µL d'enzyme + ce composé, 2 µL d'ATP 1 mM), 2 µL de γ³²P-ATP (40 μCi) et 1 µL de Cdc25C recombinante (100 ng) ou de substrats de caséine (1 μg). Les réactions sont terminées par ébullition pendant 2 min dans 20 µL de tampon Laemmli 2×. Les substrats phosphorylés sont séparés par SDS-PAGE à 18 %. Les gels sont séchés et exposés à un film radiographique pendant 3-10 min.
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.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/15766665/ [2] https://pubmed.ncbi.nlm.nih.gov/21812421/ [3] https://pubmed.ncbi.nlm.nih.gov/22351695/

Applications (Applications)

Méthodes	Biomarqueurs	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

Informations sur l'essai clinique (Clinical Trial Information)

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
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) Inhibiteur de PLK1

Poids moléculaire: 473.47

Contrôle Qualité (Quality Control)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Solubilité (Solubility)

Calculateur de molarité

Calculateur de formulation in vivo (Solution claire)

Mécanisme d'action (Mechanism of Action)

Applications (Applications)

Informations sur l'essai clinique (Clinical Trial Information)

Rigosertib Sodium (ON-01910) Inhibiteur de PLK1

Poids moléculaire: 473.47

Contrôle Qualité (Quality Control)

Culture cellulaire, traitement et concentration de travail (Cell Culture, Treatment & Working Concentration)

Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Solubilité (Solubility)

Calculateur de molarité

Calculateur de formulation in vivo (Solution claire)

Mécanisme d'action (Mechanism of Action)

Applications (Applications)

Informations sur l'essai clinique (Clinical Trial Information)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)