Name: Zileuton
Brand: Selleck Chemicals
SKU: S1443
Rating: 5 (15 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.98%

99.98

Gerelateerde doelwitten	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Overige Lipoxygenase Inhibitoren	ML355 PD146176 Nordihydroguaiaretic acid (NDGA) Malotilate Esculetin Demethylnobiletin 4',5-Dihydroxyflavone AKBA (3-O-Acetyl-11-keto-β-boswellic acid) ML351 Abietic Acid

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
RBI-1	Function assay			In vitro inhibition of 5-lipoxygenase (5-lo) from the 20000 g supernatant of RBI-1 cells, IC50=0.6μM	2066989
RBL-1	Function assay			Inhibitory concentration against 5-lipoxygenase in rat RBL-1 cells, IC50=3.2μM	8831759
basophilic leukemia cells	Function assay			Inhibitory activity against 5-lipoxygenase obtained from rat basophilic leukemia cells, IC50=0.5μM	9484493
RBL-2H3	Function assay			Inhibition of 5-lipoxygenase mediated conversion of [14C]arachidonic acid to leukotrienes in RBL-2H3 cells, IC50=0.804μM	9599246
granulocytes-type cells	Function assay			The compound was evaluated for its inhibitory activity against 5-lipoxygenase using granulocytes-type cells, IC50=2.9μM	11859001
polymorphonuclear cells	Antileukotrienic assay			Antileukotrienic activity in rat polymorphonuclear cells assessed as inhibition of LTB4 biosynthesis, IC50=0.01μM	17448575
MC9	Function assay			Inhibition of LTB4 production in mouse MC9 cells, IC50=0.55μM	18498150
MC9	Function assay			Inhibition of leukotrienes production in mouse MC9 cells	18498150
PMNL	Function assay		15 mins	Inhibition of 5-lipoxygenase in cell free S100 freshly isolated human PMNL cells assessed as inhibition of A23187-stimulated 5-LO product formation preincubated for 15 mins measured after 10 mins by HPLC analysis, IC50=0.5μM	22551629
BMM	Function assay		30 mins	Inhibition of 5-LO in mouse BMM cells assessed as formation of LTC4 after 30 mins by enzyme immunoassay, IC50=0.19μM	26432605
A549	Function assay		15 mins	Inhibition of mPGES-1 isolated from microsomes of interleukin-1 beta-stimulated human A549 cells using PGH2 as substrate preincubated for 15 mins followed by substrate addition measured after 1 min by RP-HPLC analysis, IC50=0.6μM	30053720
RAW264.7	Function assay	5 uM	24 hrs	Inhibition of LPS/IFNgamma-stimulated lipid peroxidation in mouse RAW264.7 cells at 5 uM after 24 hrs by BODIPY 581/591 C11-staining based FACS assay	30964295
RAW264.7	Function assay	5 uM	48 hrs	Protection against LPS-induced cell death in mouse RAW264.7 cells assessed as increase in cell viability at 5 uM measured after 48 hrs by MTS assay relative to control	30964295
PMNL	Function assay		5 mins	Inhibition of 5-LO in human PMNL cells assessed as reduction in leukotriene formation preincubated for 5 mins followed by thapsigargin stimulation measured after 15 mins by RP-HPLC analysis, IC50=2.31μM	31260889
HEK293	Function assay	1 uM	5 mins	Inhibition of human 5-LO transfected in HEK293 cells coexpressing FLAP assessed as reduction in leukotriene formation at 1 uM using arachidonic acid as substrate preincubated for 5 mins followed by calcium ionophore A23187/arachidonic acid addition and me	31260889
PMNL	Function assay	1 uM	5 mins	Inhibition of 5-LO in human PMNL cells assessed as reduction in leukotriene formation at 1 uM preincubated for 5 mins followed by thapsigargin stimulation measured after 15 mins by RP-HPLC analysis relative to control	31260889
BL21 (DE3)	Function assay		10 mins	Inhibition of recombinant human 5-lipoxygenase expressed in Escherichia coli BL21 (DE3) cells using arachidonic acid as substrate preincubated for 10 mins followed by susbtrate addition and measured after 10 mins by reverse phase HPLC method, IC50=0.5μM	31465225
insect cells	Function assay		5 mins	Inhibition of human recombinant 5-LOX expressed in insect cells assessed as decrease in production of 5-HPETE and 5-HETE using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition measured after 20 mins in dark by ferric io, IC50=23.9μM	31774676
RBL-2H3	Function assay			Inhibition of 5-Lipoxygenase of rat basophilic leukemia cells, IC50=0.14μM	ChEMBL
Sf21	Function assay		4 mins	Inhibition of rat 5-LOX expressed in Sf21 insect cells preincubated for 4 mins followed by AA substrate addition and measured after 4 mins by FOX assay, IC50=0.18μM	ChEMBL
RBL-2H3	Function assay			In vitro inhibition of 5-lipoxygenase in RBL-2H3 (Rat basophilic leukemia) cells, IC50=1.25μM	ChEMBL
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Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	236.29	Formule	C₁₁H₁₂N₂O₂S	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	111406-87-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	A-64077			Smiles	CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 47 mg/mL (198.9 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 47 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

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.
Clear solution	5%DMSO 1 95% of 20%Hydroxypropyl-β-cyclodextrin Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	6.250mg/ml (26.45mM)	Taking the 1 mL working solution as an example, add 50 μL of 125 mg/ml clear DMSO stock solution to 950 μL of 20%Hydroxypropyl-β-cyclodextrin and mix evenly. 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 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.000mg/ml (4.23mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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.	4.500mg/ml (19.04mM)	Taking the 1 mL working solution as an example, add 50 μL of 90 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 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.650mg/ml (2.75mM)	Taking the 1 mL working solution as an example, add 50 μL of 13 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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 Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van 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 het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

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

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

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

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	Ferroptosis 5-lipoxygenase
In vitro	Zileuton suppresses PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. This compound significantly reduces PGE2 and 6-keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. It inhibits PGE2 production in LPS-stimulated human whole blood and suppresses PGE2 and 6-keto PGF1α pleural levels in rat carrageenan-induced pleurisy.
In vivo	Zileuton significantly reduces macroscopic damage score after four weeks of treatment in rats. This compound administration significantly increases the intracolonic release of both thromboxane B2 at week 1 and prostaglandin E2 at weeks 2 and 4 in rats. It reduces the spinal cord inflammation and tissue injury, neutrophil infiltration, TNF-alpha, COX-2 and pERK1/2 expression, PGE(2) and LTB(4) production, and apoptosis in mice. This chemical significantly improves the recovery of limb function over 10 days in mice. It administrated before I/R significantly reduces the degree of renal dysfunction (urea, creatinine) and injury (AST, histology) in 5-lipoxygenase knockout mice. This compound reduces the expression of ICAM-1 and the associated PMN infiltration caused by I/R of the mouse kidney in 5-lipoxygenase knockout mice. It inhibits LTB(4) production in the peritonitis model more effectively than the LTA(4)H inhibitor, but the influx of neutrophils into the peritoneum after 1 and 2 hours is significantly higher in this compound- versus JNJ-26993135-treated mice.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/20880396/ [2] https://pubmed.ncbi.nlm.nih.gov/8984030/ [3] https://pubmed.ncbi.nlm.nih.gov/18059327/ [4] https://pubmed.ncbi.nlm.nih.gov/15266012/ [5] https://pubmed.ncbi.nlm.nih.gov/17371808/ [6] https://pubmed.ncbi.nlm.nih.gov/26235588/

Informatie klinische proef (Clinical Trial Information)

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

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT01136941	Completed	Sickle Cell Disease	Children''s Hospital Medical Center Cincinnati	September 2010	Phase 1
NCT01130688	Terminated	Chronic Myelogenous Leukemia	University of Massachusetts Worcester	January 2010	Phase 1

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Zileuton Lipoxygenase Remmer

Moleculair gewicht: 236.29

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie klinische proef (Clinical Trial Information)

Zileuton Lipoxygenase Remmer

Moleculair gewicht: 236.29

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie klinische proef (Clinical Trial Information)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)