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Clofarabine DNA/RNA Synthesis inibitore

Name: Clofarabine
Brand: Selleck Chemicals
SKU: S1218
Rating: 5 (23 reviews)

N. Cat.S1218

Clofarabine (Clolar) inibisce le attività enzimatiche della ribonucleotide reductase (RNR) (IC50 = 65 nM) e della DNA polimerasi. Questo composto induce autophagy e apoptosis.

Clofarabine DNA/RNA Synthesis inibitore Chemical Structure

Struttura chimica

Peso molecolare: 303.68

Vai a

Controllo Qualità

Lotto: Purezza: 99.90%

99.90

Target correlati	HDAC PARP ATM/ATR DNA-PK WRN Topoisomerase PPAR Sirtuin Casein Kinase eIF
Altro DNA/RNA Synthesis Inibitori	CX-5461 (Pidnarulex) B02 SCR7 Favipiravir (T-705) EED226 RK-33 BMH-21 Triapine (3-AP) Carmofur YK-4-279

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dellattività	PMID
K562 cell	Cytotoxicity assay			Compound was tested for cytotoxicity against K562 cell lines, IC50=0.003 μM	1732556
HEp-2 cell	Cytotoxicity assay			Compound was tested for cytotoxicity against HEp-2 cell lines, IC50=0.012 μM	1732556
CCRF-CEM cell lines	Cytotoxicity assay			Compound was tested for cytotoxicity against CCRF-CEM cell lines, IC50=0.05 μM	1732556
L1210 cell	Cytotoxicity assay			Compound was tested for cytotoxicity against L1210 cell lines, IC50=2.3 μM	1732556
NCI-H23	Cytotoxicity assay		5 days	Cytotoxicity against human NCI-H23 cells after 5 days by SRB assay, GI50=0.04μM	19929004
PC3	Cytotoxicity assay		5 days	Cytotoxicity against human PC3 cells after 5 days by SRB assay, GI50=0.063μM	19929004
BT549	Cytotoxicity assay		5 days	Cytotoxicity against human BT549 cells after 5 days by SRB assay, GI50=0.065μM	19929004
HCT15	Cytotoxicity assay		5 days	Cytotoxicity against human HCT15 cells after 5 days by SRB assay, GI50=0.18μM	19929004
NCI-H23	Cytostatic assay		5 days	Cytostatic activity against human NCI-H23 cells after 5 days by SRB assay, GI50=0.04μM	21711054
MT4	Cytostatic assay		5 days	Cytostatic activity against human MT4 cells after 5 days by SRB assay, GI50=0.051μM	21711054
PC3	Cytostatic assay		5 days	Cytostatic activity against human PC3 cells after 5 days by SRB assay, GI50=0.063μM	21711054
BT549	Cytostatic assay		5 days	Cytostatic activity against human BT549 cells after 5 days by SRB assay, GI50=0.065μM	21711054
A549	Cytostatic assay		5 days	Cytostatic activity against human A549 cells after 5 days by SRB assay, GI50=0.086μM	21711054
HCT116	Cytostatic assay		5 days	Cytostatic activity against human HCT116 cells after 5 days by SRB assay, GI50=0.106μM	21711054
DU145	Cytostatic assay		5 days	Cytostatic activity against human DU145 cells after 5 days by SRB assay, GI50=0.125μM	21711054
HCT15	Cytostatic assay		5 days	Cytostatic activity against human HCT15 cells after 5 days by SRB assay, GI50=0.18μM	21711054
Hs578	Cytostatic assay		5 days	Cytostatic activity against human Hs578 cells after 5 days by SRB assay, GI50=1.241μM	21711054
HL60	Cytostatic assay		48 hrs	Cytostatic activity against human HL60 cells after 48 hrs by MTT assay, IC50=0.1μM	23820572
A549	Cytostatic assay		48 hrs	Cytostatic activity against human A549 cells after 48 hrs by MTT assay, IC50=8μM	23820572
U373-MAGI	Function assay	50 nM	2 hrs	Potentiation of 5-Aza-C-induced antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as 5-Aza-C EC50 at 50 nM preincubated for 2 hrs followed by 5-Aza-C addition for 2 hrs and subsequent viral infection measu, EC50=30.4μM	27117260
U373-MAGI	Antiviral assay	50 nM	4 hrs	Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in viral infectivity at 50 nM incubated for 4 hrs prior to viral infection measured at 72 hrs post infection by flow cytometric analysis	27117260
U373-MAGI	Function assay	200 nM	6 hrs	Reduction in dGTP level in human U373-MAGI cells at 200 nM after 6 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	6 hrs	Reduction in dCTP level in human U373-MAGI cells at 200 nM after 6 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	6 hrs	Reduction in dATP level in human U373-MAGI cells at 200 nM after 6 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	50 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 50 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-C	27117260
U373-MAGI	Function assay	50 nM	2 hrs	Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 50 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in dRGU-TP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in 5-aza-dCTP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
U373-MAGI	Function assay	50 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 50 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for MG 63 (6-TG R) cells	29435139
Granta	Cytotoxicity assay		72 hrs	Cytotoxicity against human Granta cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.017μM	30176535
HL60	Cytotoxicity assay		72 hrs	Cytotoxicity against human HL60 cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.04μM	30176535
CCRF-CEM	Cytotoxicity assay		72 hrs	Cytotoxicity against human CCRF-CEM cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.044μM	30176535
RL	Cytotoxicity assay		72 hrs	Cytotoxicity against human RL cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.38μM	30176535
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Informazioni chimiche, conservazione e stabilità

Peso molecolare	303.68	Formula	C₁₀H₁₁ClFN₅O₃	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	123318-82-1	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	Clolar			Smiles	C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)F)Cl)N

Solubilità

In vitro
Lotto:

DMSO : 60 mg/mL (197.57 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

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.
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 lesperimento)

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 cè 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, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Targets/IC₅₀/Ki	Ribonucleotide reductase (Cell-free assay) 65 nM
In vitro	La Clofarabine viene trasportata efficientemente nelle cellule tramite due trasportatori di nucleosidi facilitativi o equilibrativi, hENT1 e hENT2, e un trasportatore di nucleosidi concentrativo, hCNT253. Questo composto viene fosforilato in modo graduale dalle chinasi citosoliche agli analoghi nucleotidici Clofarabine 5′-mono-, di- e trifosfato dopo l'ingresso nelle cellule, con il Clofarabine trifosfato che è la forma attiva. I Clofarabine 5′-mono-, di- e trifosfato non sono substrati per i trasportatori di nucleosidi e devono essere convertiti enzimaticamente dalla 5′-nucleotidasi alla loro forma nucleosidica defosforilata per il trasporto fuori dalla cellula. Il trifosfato di questo composto è un potente inibitore della ribonucleotide reductase (IC50 = 65 nM), presumibilmente legandosi al sito allosterico sulla subunità regolatoria. È stato anche dimostrato che agisce direttamente sui mitocondri alterando il potenziale transmembrana con il rilascio del citocromo c, del fattore induttore di apoptosi (AIF), del fattore attivante la proteasi di apoptosi 1 (APAF1) e della caspasi 9 nel citosol. Questa sostanza chimica dimostra una forte inibizione della crescita in vitro e attività citotossica (valori di IC50 = 0,028–0,29 μM) in una vasta varietà di linee cellulari di leucemia e tumori solidi. È stato dimostrato che aumenta l'attività della dCK nelle cellule HL60 e aumenta la formazione dei mono-, di- e trifosfati di ara-C nelle cellule K56236. Questo composto (10 μM) inibisce la riparazione avviata dalla 4-idroperossiciclofosfamide (4-HC), con l'inibizione che raggiunge il picco a concentrazioni intracellulari di 5 μM nei linfociti della leucemia linfocitica cronica (LLC). Esso (10 μM) combinato con la 4-idroperossiciclofosfamide (4-HC) produce una morte cellulare apoptotica più che additiva rispetto alla somma di ciascuno da solo. Questa sostanza chimica (1 μM) combinata con ara-C (10 μM) si traduce in una modulazione biochimica di ara-CTP e in un'uccisione sinergica delle cellule K562.
In vivo	La Clofarabine somministrata per via intraperitoneale ha un'attività significativa contro una vasta varietà di xenotrapianti tumorali umani impiantati sottocutaneamente in topi nudi atimici o con grave immunodeficienza combinata.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/17016426/ [2] https://pubmed.ncbi.nlm.nih.gov/11705880/ [3] https://pubmed.ncbi.nlm.nih.gov/15723262/

Informazioni sullo studio clinico

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

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT05917405	Recruiting	Acute Myeloid Leukemia in Remission	Nantes University Hospital	September 14 2023	Phase 2
NCT03609814	Completed	Hematologic Malignancies\|Nonmalignant Diseases\|Immunodeficiencies\|Hemoglobinopathies\|Genetic Inborn Errors of Metabolism\|Fanconi''s Anemia\|Thalassemia\|Sickle Cell Disease	University of California San Francisco	January 26 2016	--

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