Home Metabolism Lipoxygenase inhibitor Zileuton

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Zileuton Lipoxygenase inhibitor

제품 번호: S1443

Zileuton is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used to decrease the symptoms of asthma. This compound induces apoptosis while inhibits ferroptosis.
Zileuton Lipoxygenase inhibitor Chemical Structure

화학 구조

분자량: 236.29

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품질 관리 (Quality Control)

배치: 순도: 99.98%
99.98

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 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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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 236.29 화학식

C11H12N2O2S

 보관 (수령일로부터)
CAS 번호 111406-87-2 SDF 다운로드 원액 보관

동의어 A-64077 Smiles CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O

용해도 (Solubility)

In vitro
배치:

DMSO : 47 mg/mL (198.9 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 47 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
Ferroptosis
5-lipoxygenase
시험관 내(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.

생체 내(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.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/15266012/
  • [5] https://pubmed.ncbi.nlm.nih.gov/17371808/
  • [6] https://pubmed.ncbi.nlm.nih.gov/26235588/

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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