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Decitabine DNA Methyltransferase Remmer

Name: Decitabine
Brand: Selleck Chemicals
SKU: S1200
Rating: 5 (221 reviews)

Cat.nr.S1200

Decitabine is een DNA methyltransferase-remmer, die in DNA wordt opgenomen en resulteert in hypomethylering van DNA en intra-S-fase arrest van DNA-replicatie. Het wordt gebruikt om myelodysplastisch syndroom (MDS) te behandelen. Decitabine induceert celcyclusarrest en Apoptosis in verschillende kankercellijnen.

Decitabine DNA Methyltransferase Remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 228.21

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.90%

99.90

Gerelateerde doelwitten	HDAC JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK
Overig DNA Methyltransferase Inhibitoren	RG108 (N-Phthalyl-L-Tryptophan) SGI-1027 Zebularine (NSC 309132) GSK3685032 Gamma-Oryzanol β-thujaplicin CM272 Bobcat339 DC-05 2'-Deoxy-5-Fluorocytidine

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
Eca109	Function Assay	0.5 μM	24 h	water	modulates the gene expression of MAGE-A members	25123082
Eca109	Growth Inhibition Assay	0.5/2.5/5 μM	24/48/72 h	water	inhibits cell growth in both dose- and time- dependent manner	25123082
Eca109	Function Assay	0.5 μM	6/12/24 h	water	inhibits cell migration	25123082
Eca109	Function Assay	0.5 μM	24 h	water	inhibits cell invasion	25123082
Eca109	Growth Inhibition Assay	0.5 μM	24 h	water	induces G2/M arrest in the cell cycle	25123082
Eca109	Function Assay	0.5/1 μM	24 h	water	decreases expression of NF-κB2 and MMP2	25123082
SW1116	Growth Inhibition Assay	0.5/1/2/5 μM	48 h	DMSO	enhances the Gefitinib induced cell inhibition	24874286
LOVO	Growth Inhibition Assay	0.5/1/2/5 μM	48 h	DMSO	enhances the Gefitinib induced cell inhibition	24874286
SW1116	Function Assay	10 μM	48 h	DMSO	increases the effective at inhibiting AKT and mTOR signaling pathways combined with gefitinib	24874286
LOVO	Function Assay	10 μM	48 h	DMSO	increases the effective at inhibiting AKT and mTOR signaling pathways combined with gefitinib	24874286
SW1116	Apoptosis Assay	10 μM	48 h	DMSO	enhances Gefitinib-induced apoptosis	24874286
LOVO	Apoptosis Assay	10 μM	48 h	DMSO	enhances Gefitinib-induced apoptosis	24874286
RPMI-8226	Apoptosis Assay	1/2 μM	48/72/96 h	DMSO	induces cell apoptosis	24833108
OPM-2	Apoptosis Assay	1/2 μM	72/96/120 h	DMSO	induces cell apoptosis	24833108
JJN3	Apoptosis Assay	0.5/1 μM	24/48 h	DMSO	induces cell apoptosis	24833108
NCI-H929	Apoptosis Assay	1/2 μM	72/96/120 h	DMSO	induces cell apoptosis	24833108
RPMI-8226	Growth Inhibition Assay	1/2 μM	24/48/72 h	DMSO	affects cell cycle progression negatively	24833108
OPM-2	Growth Inhibition Assay	1/2 μM	24/48/72 h	DMSO	affects cell cycle progression negatively	24833108
JJN3	Growth Inhibition Assay	0.5/1 μM	24/48/72 h	DMSO	affects cell cycle progression negatively	24833108
NCI-H929	Growth Inhibition Assay	1/2 μM	24/48/72 h	DMSO	affects cell cycle progression negatively	24833108
HeLa	Kinase Assay				Ki=1000–5000 μM for hENT1	24780098
HeLa	Kinase Assay				Ki=5.6 ± 0.5 μM for hENT2	24780098
HeLa	Kinase Assay				Ki=21.6 ± 3.0 μM for hCNT1	24780098
HeLa	Kinase Assay				Ki=14.4 ± 4.6 μM for hCNT3	24780098
NB4	Function Assay	2.5/5/7.5/10 μM	24 h	DMSO	increasea the expression of precursor miR-125a	24484870
CD4+ CD25− T	Function Assay	1/5 μM			reduceS global DNA methylation	24476360
BV-173	Apoptosis Assay	0.25/0.5/0.75/1 μM	48/72/96 h	PBS	induces cell apoptosis in both dose- and time- dependent manner	24423613
ML-1	Apoptosis Assay	0.25/0.5/0.75/1 μM	48/72/96 h	PBS	induces cell apoptosis in both dose- and time- dependent manner	24423613
HL-60	Apoptosis Assay	0.25/0.5/0.75/1 μM	48/72/96 h	PBS	induces cell apoptosis in both dose- and time- dependent manner	24423613
KG-1a	Apoptosis Assay	0.25/0.5/0.75/1 μM	48/72/96 h	PBS	induces cell apoptosis in both dose- and time- dependent manner	24423613
BV-173	Function Assay	250/500nM	48 h	PBS	induces delayed and sustained ROS increase	24423613
CEM	Function Assay	250/500nM	48 h	PBS	induces delayed and sustained ROS increase	24423613
HL-60	Function Assay	250/500nM	48 h	PBS	induces delayed and sustained ROS increase	24423613
ML-1	Function Assay	250/500nM	48 h	PBS	induces delayed and sustained ROS increase	24423613
DLD-1	Function Assay	250/500nM	48 h	PBS	do not induces delayed and sustained ROS increase	24423613
HCT-116	Function Assay	250/500nM	48 h	PBS	do not induces delayed and sustained ROS increase	24423613
U937-A/E-9/14/18	Apoptosis Assay	0.01/0.1/1/10 μM	48 h		induces cell apoptosis in a dose-dependent manner	24300456
HT29	Growth Inhibition Assay		72 h		IC50=1400±179 μM	24172061
SW48	Growth Inhibition Assay		72 h		IC50=15.2±6.2 μM	24172061
HCT116	Growth Inhibition Assay		72 h		IC50=1.7±0.4 μM	24172061
HepG2	Function Assay	0.5/1 μM	24 h	DMSO	up-regulated the relative OCTN2 mRNA and protein expression	24146874
LS174T	Function Assay	0.5/1 μM	24 h	DMSO	lead to an increase of OCTN2 levels	24146874
HepG2	Apoptosis Assay	1/10/100 μM	7 d	DMSO	induces cell apoptosis in a dose-dependent manner	24146874
LS174T	Apoptosis Assay	1/10/100 μM	7 d	DMSO	induces cell apoptosis in a dose-dependent manner	24146874
QBC-939	Apoptosis Assay	1/10/100 μM	7 d	DMSO	induces cell apoptosis in a dose-dependent manner	24146874
U251	Apoptosis Assay	1/10/100 μM	7 d	DMSO	induces cell apoptosis in a dose-dependent manner	24146874
HL-60	Growth Inhibition Assay	1 μM	48 h		increases G2-phase cell fraction	24000324
MDA‑MB‑453	Function Assay	0.2/1 μM	72 h		causes re-expression of claudin 1	23844228
HCC1569	Function Assay	0.2/1 μM	72 h		causes re-expression of claudin 1	23844228
BT‑474	Function Assay	0.2/1 μM	72 h		causes re-expression of claudin 1	23844228
AGS	Apoptosis Assay	5/10/20/50 μM	48 h	DMSO	inhibits the cell viability	23582784
A549	Apoptosis Assay	5/10/20/50 μM	48 h	DMSO	inhibits the cell viability	23582784
AGS	Growth Inhibition Assay	5/10/20/50 μM	48 h	DMSO	induces G2/M phase arrest	23582784
Kasumi-1	Apoptosis Assay	0.5 μM	48 h		decreases the cell viability co-treated with Tf-NP-sc	23493348
OCI-AML3	Apoptosis Assay	2.5 μM	48 h		decreases the cell viability co-treated with Tf-NP-sc	23493348
MV4-11	Apoptosis Assay	2.5 μM	48 h		decreases the cell viability co-treated with Tf-NP-sc	23493348
NK	Cytotoxity Assay	0.02-20 μM	5 d		decreases the cytolytic activity of NK cells at intermediate concentrations resulting in a U-shaped dose–response curve	23328088
NK	Apoptosis Assay	0.02-20 μM	5 d		decrease NK cell proliferation and viability as the concentration increased	23328088
NK	Function Assay	0.01-20 μM	5 d		causes hypomethylation of NK cells in a dose–response	23328088
MOLT4/DNR	Function Assay	5 μM	4 d		reduces ABCB1 mRNA expression	23060570
Jurkat/DOX	Function Assay	5 μM	4 d		reduces ABCB1 mRNA expression	23060570
MOLT4/DNR	Growth Inhibition Assay	5 μM	4 d		reduces the IC50 value for daunorubicin sensitivity	23060570
Jurkat/DOX	Growth Inhibition Assay	5 μM	4 d		reduces the IC50 value for daunorubicin sensitivity	23060570
ccRCC	Apoptosis Assay	0.01-10μM	72 h	DMSO	has minimal effect on cell proliferation	22826467
TNBC	Apoptosis Assay	0.01-10μM	72 h	DMSO	has minimal effect on cell proliferation	22826467
A498	Apoptosis Assay	0.01-10μM	72 h	DMSO	induces synergistic responses with romidepsin	22826467
KIJ265T	Apoptosis Assay	0.01-10μM	72 h	DMSO	induces synergistic responses with romidepsin	22826467
MDA-231	Apoptosis Assay	0.01-10μM	72 h	DMSO	induces synergistic responses with romidepsin	22826467
BT-20	Apoptosis Assay	0.01-10μM	72 h	DMSO	induces synergistic responses with romidepsin	22826467
U937	Growth Inhibition Assay	5-20 μM	24/48/72 h		induces a decrease in cell viability in a concentration- and time-dependent manner	22767021
HL60	Growth Inhibition Assay	5-20 μM	24/48/72 h		induces a decrease in cell viability in a concentration- and time-dependent manner	22767021
U937	Apoptosis Assay	15 μM	24/48/72 h		induces cell apoptosis	22767021
HL60	Apoptosis Assay	15 μM	24/48/72 h		induces cell apoptosis	22767021
LS411N	Apoptosis Assay	0.5 μM	72 h		increases Fas mRNA level	22461695
MDA-MB-231	Apoptosis Assay	10 μM	48 h		reduces cell viability in a dose-dependent manner	21887697
MCF-7	Apoptosis Assay	10 μM	48 h		reduces cell viability in a dose-dependent manner	21887697
A375	Growth Inhibition Assay	0.5 μM	1/5/8 d		inhibits proliferation and induces differentiation of melanoma cells	21796622
SKMEL1	Growth Inhibition Assay	0.5 μM	1/5/8 d		inhibits proliferation and induces differentiation of melanoma cells	21796622
SKMEL3	Growth Inhibition Assay	0.5 μM	1/5/8 d		inhibits proliferation and induces differentiation of melanoma cells	21796622
SKMEL28	Growth Inhibition Assay	0.5 μM	1/5/8 d		inhibits proliferation and induces differentiation of melanoma cells	21796622
MeWo	Growth Inhibition Assay	0.5 μM	1/5/8 d		inhibits proliferation and induces differentiation of melanoma cells	21796622
B16	Growth Inhibition Assay	0.5 μM	1/5/8 d		inhibits proliferation and induces differentiation of melanoma cells	21796622
Ly 1	Growth Inhibition Assay		24 h		IC50=7.3 μM	21772049
Ly 7	Growth Inhibition Assay		24 h		IC50=10.7 μM	21772049
Su-DHL6	Growth Inhibition Assay		24 h		IC50＞20 μM	21772049
Ly 10	Growth Inhibition Assay		24 h		IC50＞20 μM	21772049
RIVA	Growth Inhibition Assay		24 h		IC50＞20 μM	21772049
Su-DHL2	Growth Inhibition Assay		24 h		IC50＞20 μM	21772049
Ly 1	Growth Inhibition Assay		48 h		IC50=0.34 μM	21772049
Ly 7	Growth Inhibition Assay		48 h		IC50=0.025 μM	21772049
Su-DHL6	Growth Inhibition Assay		48 h		IC50＞20 μM	21772049
Ly 10	Growth Inhibition Assay		48 h		IC50=1.8 μM	21772049
RIVA	Growth Inhibition Assay		48 h		IC50＞20 μM	21772049
Su-DHL2	Growth Inhibition Assay		48 h		IC50=17.4 μM	21772049
Ly 1	Growth Inhibition Assay		72 h		IC50=0.01 μM	21772049
Ly 7	Growth Inhibition Assay		72 h		IC50=0.018 μM	21772049
Su-DHL6	Growth Inhibition Assay		72 h		IC50=1.6 μM	21772049
Ly 10	Growth Inhibition Assay		72 h		IC50=1.2 μM	21772049
RIVA	Growth Inhibition Assay		72 h		IC50＞20 μM	21772049
Su-DHL2	Growth Inhibition Assay		72 h		IC50=11.2 μM	21772049
U373-MAGI	Antiviral assay	0.25 to 8 uM	2 to 72 hrs		Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in U5-gag level at 0.25 to 8 uM after 2 to 72 hrs by qPCR method	27117260
U373-MAGI	Antiviral assay	0.25 to 8 uM	2 to 72 hrs		Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in gag level at 0.25 to 8 uM after 2 to 72 hrs by qPCR method	27117260
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	228.21	Formule	C₈H₁₂N₄O₄	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	2353-33-5	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	Deoxycytidine, 5-aza-2'-deoxycytidine, 5-AZA-dC, 5-aza-CdR,NSC 127716			Smiles	C1C(C(OC1N2C=NC(=NC2=O)N)CO)O

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 45 mg/mL (197.18 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : 22.5 mg/mL

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.
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.	10.000mg/ml (43.82mM)	Taking the 1 mL working solution as an example, add 10 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.

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 (Mechanism of Action)

Targets/IC₅₀/Ki	DNA methylation (HL-60, KG1a cells)
In vitro	Decitabine remt de celgroei op een dosis- en tijdsafhankelijke manier met IC50's van ongeveer 438 nM en 43,8 nM voor respectievelijk 72 uur en 96 uur blootstelling in HL-60 en KG1a leukemische cellen. Een recente studie toont aan dat deze verbinding een hoge anti-proliferatieve en pro-apoptotische activiteit vertoont tegen anaplastisch grootcellig lymfoom (ALCL), en de opname van [³H]–thymidine in KARPAS-299 cellen remt met een EC50 van 0,49 μM.
Kinase Assay	DNA-synthese analyse
Kinase Assay	De snelheid van DNA-synthese wordt gemeten door de incorporatie van radioactief thymidine in DNA. HL-60 en KG1a cellen worden gesuspendeerd in 2 ml RPMI-medium met 10% foetaal serum in 6-wells (35 mm diameter) schalen en gedurende 48 uur geïncubeerd met verschillende concentraties van de overeenkomstige geneesmiddelen (geneesmiddelen worden gelijktijdig toegevoegd). Na 48 uur wordt 0,5 μCi [³H] thymidine (6,7 Ci/mmol) aan elke well toegevoegd en gedurende nog eens 24 uur geïncubeerd. De cellen worden op GF/C glasvezelfilters (2,4 cm diameter) geplaatst, gewassen met koud 0,9% NaCl, 5% koud trichloorazijnzuur en ethanol. De filters die het DNA bevatten, worden vervolgens gedroogd, in EcoLite scintillatievloeistof (ICN) geplaatst en de radioactiviteit wordt gemeten met behulp van een Beckman LS 6000IC scintillatieteller. De IC50 wordt gedefinieerd als de concentratie van het geneesmiddel die 50% van de DNA-synthese van de leukemische cellijnen remt, afgeleid van de dosis-respons curve.
In vivo	In een ALK+ KARPAS-299 muis xenograft model veroorzaakt Decitabine in een dosis van 2,5 mg/kg een verhoogde Apoptosis en verminderde proliferatie van tumorcellen, en resulteert het ook in demethylering van tumoronderdrukker p16INK4A.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/12620295/ [2] https://pubmed.ncbi.nlm.nih.gov/22687603/

Toepassingen (Applications)

Methoden	Biomarkers	PMID
Western blot	Survivin / Bcl-2 / p53 / c-Myc / DNMT1 p-AKT / AKT / p-GSK3β / GSK3β / p-Myc / Myc / p-P70 / P70 / p-4EBP-1 / 4EBP-1 / PTEN phospho-p38 / p38 / phospho-NFκB / NFκB p-JAK1 / JAK1 / p-JAK2 / JAK2 / p-STAT3 / STAT3 E-cadherin / N-cadherin / Snail / MMP-2 / MMP-9 / Bcl-2 / Bax	26384351
Immunofluorescence	DNMT1 E-cadherin / MMP-9	21303982
Growth inhibition assay	Cell viability	26384351

Informatie over klinische proeven (Clinical Trial Information)

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT06291285	Not yet recruiting	Healthy Volunteers	Novo Nordisk A/S	February 27 2024	Phase 1
NCT05960773	Recruiting	Mesothelioma\|Malignant Mesothelioma (MM)\|Early-stage Mesothelioma\|Subclinical Mesothelioma\|BRCA1-Associated Protein-1 (BAP1) Mutations\|Early-stage BAP1-associated Malignancies	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	January 31 2024	Phase 2
NCT05835011	Terminated	Myelodysplastic Syndromes	Astex Pharmaceuticals Inc.	July 14 2023	Phase 2
NCT05816356	Recruiting	Healthy	EpiDestiny Inc.\|Worldwide Clinical Trials	March 24 2023	Phase 1

Veelgestelde vragen (Frequently Asked Questions)

Vraag 1:
Is it a racemic mixture or a monomer?

Antwoord:
Its S1200 is R form.

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):