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

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.52%

99.52

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

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dell'attività	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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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	473.47	Formula	C₂₁H₂₄NNaO₈S	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	1225497-78-8	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	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+]

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 94 mg/mL (198.53 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : 94 mg/mL

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (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.
Saggio chinasico	Saggi enzimatici in vitro per PLK1
Saggio chinasico	PLK1 ricombinante (10 ng) viene incubata con diverse concentrazioni di Rigosertib (ON-01910) in una miscela di reazione da 15 µL (50 mM HEPES, 10 mM MgCl₂, 1 mM EDTA, 2 mM Ditiotreitolo, 0,01% NP-40 [pH 7,5]) per 30 minuti a temperatura ambiente. Le reazioni chinasiche vengono eseguite per 20 minuti a 30 °C in un volume di 20 µL (15 µL di enzima + questo composto, 2 µL di ATP 1 mM), 2 µL di γ³²P-ATP (40 μCi) e 1 µL di Cdc25C ricombinante (100 ng) o substrati di caseina (1 μg). Le reazioni vengono terminate facendo bollire per 2 minuti in 20 µL di tampone Laemmli 2×. I substrati fosforilati vengono separati mediante SDS-PAGE al 18%. I gel vengono essiccati ed esposti a pellicola a raggi X per 3-10 minuti.
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.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/15766665/ [2] https://pubmed.ncbi.nlm.nih.gov/21812421/ [3] https://pubmed.ncbi.nlm.nih.gov/22351695/

Applicazioni (Applications)

Metodi	Biomarcatori	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

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
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) PLK1 Inhibitor

Struttura chimica

Peso molecolare: 473.47

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Rigosertib Sodium (ON-01910) PLK1 Inhibitor

Struttura chimica

Peso molecolare: 473.47

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro (Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)