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Fludarabine STAT1-remmer

Cat.nr.S1491

Fludarabine is een STAT1-activatie-remmer die een specifieke uitputting van STAT1-eiwit (en mRNA) veroorzaakt, maar niet van andere STATs. Het is ook een DNA-synthese-remmer in vasculaire gladde spiercellen. Fludarabine induceert apoptose.

Fludarabine STAT remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 285.23

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Kwaliteitscontrole

Batch: Zuiverheid: 99.96%

99.96

Gerelateerde doelwitten	EGFR JAK Pim
Overig STAT Inhibitoren	Napabucasin (BBI608) Stattic NSC 74859 (S3I-201) Cryptotanshinone (Tanshinone C) C188-9 (TTI-101) SH-4-54 BP-1-102 AS1517499 Nifuroxazide HO-3867

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
Jeko-1	Function Assay	20 μM	24 h		inhibits expression of IDO	25940712
MV-4-11	Apoptosis Assay	2.5 μM	48 h		induces apoptosis slightly	25111583
THP-1	Apoptosis Assay	2.5 μM	48 h		induces apoptosis slightly	25111583
MOLM 13	Apoptosis Assay	2.5 μM	48 h		induces apoptosis slightly	25111583
KBM3/Bu2506	Apoptosis Assay	2.5 μM	48 h		induces apoptosis slightly	25111583
Nalm-6	Growth Inhibition Assay				IC50=18 μM	25061101
Reh	Growth Inhibition Assay				IC50=30 μM	25061101
U2937	Growth Inhibition Assay				IC50=16 μM	25061101
Mec-1	Growth Inhibition Assay				IC50＞500 μM	25061101
RPMI-8226	Growth Inhibition Assay				IC50=500 μM	25061101
Molt-4	Growth Inhibition Assay				IC50=180 μM	25061101
Nalm-6-FluR	Growth Inhibition Assay				IC50=250 μM	25061101
Raji	Function Assay	3 μM	24/48/72 h		induces accumulations of p53, p63 and p73	24940695
PBMC	Function Assay	50/100 μM	24 h	DMSO	inhibits STAT1 phosphorylation	24911872
MDA-231	Function Assay	100 μM	24 h	DMSO	decreases IDO expression	24911872
624.38mel	Function Assay	50 μM	24 h	DMSO	decreases IDO expression	24911872
MDA-231	Function Assay	50-200 μM	24 h	DMSO	inhibits IDO activity independently of mRNA levels	24911872
624.38mel	Function Assay	50-200 μM	24 h	DMSO	inhibits IDO activity independently of mRNA levels	24911872
HMECs	Function Assay	100 μM	36 h		inhibits IFNγ and LPS induced STAT1 phosphorylation and IRF1 expression	24211327
HMECs	Function Assay	100 μM	36 h		inhibits IFNα mediated phosphorylation of STAT1 and STAT3, but not of STAT2	24211327
BJAB	Apoptosis Assay	5 μM	24 h		induces cell apoptosis	24057147
I-83	Apoptosis Assay	5 μM	24 h		induces cell apoptosis	24057147
NALM6	Apoptosis Assay	5 μM	24 h		induces cell apoptosis	24057147
DU-145	Growth Inhibition Assay	0-10 μg/ml	48 h		inhibits cell growth in a dose-dependent manner	23734815
Nalm-6	Function Assay	10 μM	1/2/4 h		induces autophagy	23681223
Reh	Function Assay	10 μM	1/2/4 h		induces autophagy	23681223
Nalm-6	Growth Inhibition Assay				IC50 ∼10 μM	23681223
Reh	Growth Inhibition Assay				IC50 ∼10 μM	23681223
HEC1A	Growth Inhibition Assay	100-500 μM	24 h		inhibits cell growth in a dose-dependent manner	23595697
AN3CA	Growth Inhibition Assay	100-500 μM	24 h		inhibits cell growth in a dose-dependent manner	23595697
HEC50B	Growth Inhibition Assay	100-500 μM	24 h		inhibits cell growth slightly	23595697
HEC1A	Apoptosis Assay	20/100 μM	24 h		induces apoptosis in a dose-dependent manner	23595697
AN3CA	Apoptosis Assay	20/100 μM	24 h		induces apoptosis in a dose-dependent manner	23595697
HEC50B	Apoptosis Assay	20/100 μM	24 h		induces apoptosis slightly	23595697
EHEB	Apoptosis Assay	40 μM	24 h		induces apoptosis	23497075
A549	Growth Inhibition Assay				IC50=15.7±2.8 µM	23377192
A549 GAPDH-deficient	Growth Inhibition Assay				IC50=18.5±2.3 µM	23377192
CLL	Apoptosis Assay	10 μM	24-96 h		induces apoptotic cell death	22207686
MEC1	Apoptosis Assay	100 μM	72 h		induces apoptosis significantly	22132973
U937	Apoptosis Assay	0.8 μM	4-48 h		induces apoptosis slightly	22074700
U937	Apoptosis Assay	1 μM	96 h		induces apoptosis slightly	22023523
Daudi	Apoptosis Assay	20 μM	96 h		induces apoptosis slightly	22023523
J45.01	Apoptosis Assay	1 μM	96 h		induces apoptosis slightly	22023523
RPMI 8226	Growth Inhibition Assay				IC50=25.9 ± 3.7 μM	21948264
CEM	Growth Inhibition Assay				IC50=2.4 ± 0.4 μM	21948264
Raji	Growth Inhibition Assay				IC50=0.47 ± 0.04 μM	21948264
U937	Growth Inhibition Assay				IC50=0.24 ± 0.04 μM	21948264
K562	Growth Inhibition Assay				IC50=0.44 ± 0.05 μM	21948264
NALM-6	Apoptosis Assay	10 μM	24 h		induces cell apoptosis slightly	21699383
JMV-3	Apoptosis Assay	10 μM	24 h		induces cell apoptosis slightly	21699383
EHEB	Function Assay	5-50 μM	24 h		decreases p21 expression significantly	21168391
JVM-2	Function Assay	30 μM	24 h		decreases p21 expression	21168391
KBM3/Bu2506	Growth Inhibition Assay				IC20=0.67 µM	20933509
KBM3/Bu2506	Growth Inhibition Assay	0.6 μM	24 h		increases the cell fraction in S-phase	20933509
MDA-MB-231	Growth Inhibition Assay				IC50=4.0 μM	20447390
MCF-7	Growth Inhibition Assay				IC50=15.0 μM	20447390
HLE-B3	Function Assay	25 μM	48 h		blocks IFN-γ–induced STAT1 phosphorylation and IDO expression	20435158
K562	Growth Inhibition Assay		72 h		IC50=3.3 nM	20307198
BW-225	Growth Inhibition Assay				IC20=1.37 ×10−8 μM	18661380
OH-65	Growth Inhibition Assay				IC20=1.37 ×10−8 μM	18661380
GR-145	Growth Inhibition Assay				IC20=2.74 × 10−8 μM	18661380
A549	Growth Inhibition Assay				IC20=5.48 × 10−8 μM	18661380
CaSki	Growth Inhibition Assay				IC20=1.37 × 10−7 μM	18661380
ZMK-1	Growth Inhibition Assay				IC20=1.37 × 10−6 μM	18661380
SKW6.4	Apoptosis Assay	0.01-10 μM	24/48 h		induces cell death in both time- and dose- dependent manner	18092340
RPMI 8226	Growth Inhibition Assay		24 h		IC50=1.54 μM	17976186
MM.1S	Growth Inhibition Assay		48 h		IC50=13.48 μM	17976186
MM.1R	Growth Inhibition Assay		48 h		IC50=33.79 μM	17976186
U937	Growth Inhibition Assay				IC50=3,200 ± 560 nM	15930361
CLL5	Antitumor assay		48 hrs		Antitumor activity against CLL5 cells isolated from CLL patient assessed as cell viability after 48 hrs by FACS analysis, EC50 = 0.16 μM.	24673739
K562	Cytotoxicity assay		72 hrs		Cytotoxicity against human paclitaxel-resistant K562 cells after 72 hrs by MTT assay, IC50 = 0.26 μM.	20605656
CLL3	Antitumor assay		48 hrs		Antitumor activity against CLL3 cells isolated from CLL patient assessed as cell viability after 48 hrs by FACS analysis, EC50 = 0.35 μM.	24673739
CLL4	Antitumor assay		48 hrs		Antitumor activity against CLL4 cells isolated from CLL patient assessed as cell viability after 48 hrs by FACS analysis, EC50 = 0.64 μM.	24673739
CEM-DNR-B	Cytotoxicity assay		72 hrs		Cytotoxicity against human CEM-DNR-B cells after 72 hrs by MTT assay, IC50 = 1.01 μM.	20605656
primary CLL	Cytotoxicity assay				Cytotoxicity against human primary CLL cells, LD50 = 1.1 μM.	25148392
CLL6	Antitumor assay		48 hrs		Antitumor activity against CLL6 cells isolated from CLL patient assessed as cell viability after 48 hrs by FACS analysis, EC50 = 1.6 μM.	24673739
CLL2	Antitumor assay		48 hrs		Antitumor activity against CLL2 cells isolated from CLL patient assessed as cell viability after 48 hrs by FACS analysis, EC50 = 2.66 μM.	24673739
HCT116	Cytotoxicity assay		72 hrs		Cytotoxicity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 6.6 μM.	25462277
PBMC	Cytotoxicity assay		48 hrs		Cytotoxicity against patient PBMC after 48 hrs by CellTitre-Blue assay in presenc of mouse M210B4 cells, IC50 = 10 μM.	25562417
CHO	Function assay				Binding affinity determined by displacement of specific binding of [125I]N-(4-amino-3-iodophenethyl)-adenosine in membranes of CHO cells stably transfected with the rat adenosine A3 receptor, Ki = 10.4 μM.	7707320
JVM2	Antitumor assay				Antitumor activity against human JVM2 cells assessed as cell viability after 48 hrs by FACS analysis, EC50 = 10.4 μM.	24673739
HeLa	Antitumor assay				Antitumor activity against human HeLa cells assessed as cell viability by MTT assay, EC50 = 16 μM.	24673739
CLL1	Antitumor assay		48 hrs		Antitumor activity against CLL1 cells isolated from CLL patient assessed as cell viability after 48 hrs by FACS analysis, EC50 = 17.1 μM.	24673739
CEM	Cytotoxicity assay		72 hrs		Cytotoxicity against human CEM cells after 72 hrs by MTT assay, IC50 = 19.49 μM.	20605656
T47D	Cytotoxicity assay		72 hrs		Cytotoxicity against human T47D cells after 72 hrs by SRB assay, IC50 = 46.2 μM.	25462277
A549	Cytotoxicity assay		72 hrs		Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 47.44 μM.	20605656
CCRF-CEM	Function assay	10 uM	1 to 60 mins		Drug transport in human CCRF-CEM cells assessed as ENT1-mediated uptake at 10 uM after 1 to 60 mins by liquid scintillation counting analysis	23388705
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH 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
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 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
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
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
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SK-N-SH cells	29435139
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Daoy	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for Daoy cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D caspase screen for TC32 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
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 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
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
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 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
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 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
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for RD cells	29435139
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	285.23	Formule	C₁₀H₁₂FN₅O₄	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	21679-14-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	FaraA, Fludarabinum, NSC 118218			Smiles	C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)O)F)N

Oplosbaarheid

In vitro
Batch:

DMSO : 57 mg/mL (199.83 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

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	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	4.000mg/ml (14.02mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	8.000mg/ml (28.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 160 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. 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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met 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 de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

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

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

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. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC₅₀/Ki	STAT1 (Vascular smooth muscle cells)
In vitro	Fludarabine remt efficiënt de proliferatie van RPMI 8226 cellen met een IC50 van 1,54 μg/mL. De IC50 van deze verbinding tegen MM.1S en MM.1R cellen is respectievelijk 13,48 μg/mL en 33,79 μg/mL. Daarentegen zijn U266 cellen resistent tegen deze chemische stof met een IC50 van 222,2 μg/mL. Deze verbinding leidt tot een verhoogd aantal cellen in de G1-fase van de celcyclus, vergezeld van een gelijktijdige reductie van cellen in de S-fase van de celcyclus op een tijdsafhankelijke manier. Het induceert een celcyclusblokkade en triggert apoptose in MM-cellen. Het triggert tijdsafhankelijke splitsing van caspase-8, -9 en -3, -7, gevolgd door PARP-splitsing. Het verhoogt de expressie van Bax op een tijdsafhankelijke manier, terwijl de expressie van Bak niet verandert. Na blootstelling aan deze chemische stof gedurende 12 uur vertonen RPMI 8226 cellen een verlies van membraanpotentiaal, waarbij 61,05% van de cellen lage fluorescentie van rhodamine 123 vertoont, vergeleken met 8,62% van de cellen in de onbehandelde controle. Om de oplosbaarheid te verbeteren, wordt het geformuleerd als het monofosfaat (F-ara-AMP, fudarabine), dat onmiddellijk en kwantitatief gedefosforyleerd wordt tot het moedernucleoside bij intraveneuze infusie. Binnen de cellen vindt herfosforylatie plaats, wat leidt tot fuoroadenine arabinoside trifosfaat (F-ara-ATP), de belangrijkste cytotoxische metaboliet van F-ara-A. Het kan ook pro-inflammatoire stimulatie van monocytaire cellen induceren, zoals geëvalueerd door verhoogde expressie van ICAM-1 en IL-8 afgifte. Deze verbinding beïnvloedt de groei van eierstokkankercellijnen niet, terwijl het een duidelijke en dosisafhankelijke remming van proliferatie in melanoomcellijnen induceert. Het is een remmer van STAT1 die STAT1 specifiek vermindert zonder andere STAT-familieleden te beïnvloeden. Naast cytoplasmatische accumulatie induceert herhaaldelijk laaggedoseerd cisplatine (RLDC) HMGB1-expressie, die sterk wordt onderdrukt door STAT1-knockdown. Consistent onderdrukt deze chemische stof HMGB1-expressie tijdens RLDC-behandeling dosisafhankelijk in RLDC-behandelde nierbuiscellen.
In vivo	Tumoren behandeld met PBS groeien snel tot ongeveer 10 keer hun oorspronkelijke volume in 25 dagen, terwijl de tumoren in de Fludarabine bij 40 mg/kg minder dan 5 keer toenemen. Een significant antitumor effect van 40 mg/kg van deze verbinding op RPMI8226 tumorgroei wordt aangetoond. RPMI8226 tumoren behandeld met 40 mg/kg van deze chemische stof op dag 10 vertonen een toename van apoptotische kernen. Deze verbinding is effectief in het onderdrukken van RPMI8226 myeloom xenografts in SCID muizen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/17976186/ [2] https://pubmed.ncbi.nlm.nih.gov/10428391/ [3] https://pubmed.ncbi.nlm.nih.gov/16546701/ [4] https://pubmed.ncbi.nlm.nih.gov/8983288/ [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240827/

Toepassingen

Methoden	Biomarkers	PMID
Western blot	procaspase-9 / procaspase-3 p-p53 / p53 STAT1	27223263
Immunofluorescence	α-SMA / Vimentin	28322315
Growth inhibition assay	Cell viability	24956101

Informatie over klinische proeven

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT05390814	Recruiting	Primary Central Nervous System Lymphoma	Assistance Publique - Hôpitaux de Paris	December 18 2023	Phase 1
NCT05201183	Withdrawn	Acute Myeloid Leukemia\|Chronic Myeloid Leukemia\|Acute Lymphocytic Leukemia\|Myelodysplastic Syndromes	Naoyuki G. Saito M.D. Ph.D.\|Indiana University	October 2023	Phase 1\|Phase 2
NCT05917405	Recruiting	Acute Myeloid Leukemia in Remission	Nantes University Hospital	September 14 2023	Phase 2

Technische ondersteuning

Gebruiksaanwijzing

Tel: +1-832-582-8158 Ext:3

Als u nog andere vragen heeft, laat dan een bericht achter.

Veelgestelde vragen

Vraag 1:
how to re-suspend and deliver it for in vivo experiments?

Antwoord:
For S1491, we tested a vehicle: 30% Propylene glycol, 5% Tween 80, 65% D5W that you can resuspend this compound in at up to 30mg/ml. It is a suspension and can only be given via oral gavage.

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