Last update 01 Nov 2024

FLAP

Last update 01 Nov 2024

Basic Info

Synonyms

ALOX5AP, arachidonate 5-lipoxygenase activating protein, Arachidonate 5-lipoxygenase-activating protein

+ [4]

Introduction

Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.

Drugs associated with FLAP

Atuliflapon

Target

FLAP

Mechanism

FLAP inhibitors

Active Org.

AstraZeneca PLC [+2]

Originator Org.

AstraZeneca PLC

Active Indication

Asthma [+2]

Inactive Indication

Coronary Artery Disease

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AM679

Target

FLAP

Mechanism

FLAP inhibitors

Active Org.

Amira Pharmaceuticals, Inc.

Originator Org.

Amira Pharmaceuticals, Inc.

Active Indication

Asthma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ALR-27

Target

FLAP

Mechanism

FLAP inhibitors

Active Org.

Università degli Studi di Napoli Federico II

Originator Org.

Università degli Studi di Napoli Federico II

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with FLAP

NCT05251259 / RecruitingPhase 2

A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of Atuliflapon Given Orally Once Daily for Twelve Weeks in Adults With Moderate to Severe Uncontrolled Asthma

This is a randomised, placebo-controlled, double-blind study to assess the efficacy and safety of Atuliflapon administered once daily over a 12-week treatment period to adult participants with moderate to severe uncontrolled asthma.

Start Date27 Jan 2022

Sponsor / Collaborator

AstraZeneca PLC

NCT04601467 / RecruitingPhase 2IIT

PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

This is a multi-center study conducted at 13 sites in 3 countries (Singapore, New Zealand, and the Australia). Approximately 260 patients with an acute myocardial infarction (AMI) will be randomized in a ratio of 1:1 ratio to receive AZD5718 125 mg or placebo for 12 months.

Start Date12 Jul 2021

Sponsor / Collaborator

AstraZeneca PLC

NCT04734275 / CompletedPhase 1

A Randomised, Single-dose, Open-label, Single-centre, Crossover Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD5718 in Fasted and Fed State in Healthy Volunteers

This study will be a randomised, open-label, 3-period, 3-treatment, single-dose, crossover study in healthy subjects The study will be performed at a single study centre in the United Kingdom.

Start Date01 Feb 2021

Sponsor / Collaborator

AstraZeneca PLC

[+1]

100 Clinical Results associated with FLAP

100 Translational Medicine associated with FLAP

0 Patents (Medical) associated with FLAP

750

Literatures (Medical) associated with FLAP

01 Aug 2024·Prostaglandins & Other Lipid Mediators

Zerumbone exhibits anti-inflammatory effects by suppressing eicosanoid signaling: Evidence from LPS-induced peripheral blood leukocytes

Article

Author: Nair, Devika ; Acharya, Pooja ; Zarei, Mehrdad ; Uppin, Vinayak ; Talahalli, Ramaprasad ; Kempaiah, Bettadaiah

Zerumbone, a sesquiterpene isolated from Zingiber zerumbet, has many bioactivities, exhibiting anti-inflammatory properties. However, the effect of zerumbone on the eicosanoid signaling pathway has yet to be examined. Here, we deciphered the anti-eicosanoid properties of zerumbone isolated from ginger. The molecular interaction between zerumbone and eicosanoid metabolizing enzymes (COX-2, 5-LOX, FLAP, and LTA₄-hydrolase) and receptors (EP-4, BLT-1, and ICAM-1) along with NOS-2 were assessed using Auto-Dock 4.2 and visualized by chimera and Liggplot⁺ software. Further, the leukocytes were treated with zerumbone (1-20 μM) and activated using bacterial lipopolysaccharide (LPS-10 nM). The oxidative stress (OS) markers, antioxidant enzymes, and the eicosanoid pathway mediators such as COX-2, 5-LOX, BLT-1, and EP-4 were assessed. The molecular interaction of zerumbone with eicosanoids showed a higher binding affinity with mPGES-1, followed by NOS-2, FLAP, COX-2, LTA-4-hydrolase, and BLT-1. The concentration of 5 μM zerumbone effectively prevented the generation of reactive oxygen species (ROS) and nitric oxide (NO). Likewise, zerumbone significantly (p<0.05) inhibited COX-2, 5-LOX, NOS-2, EP-4, BLT-1, and ICAM-1 expression in LPS-induced peripheral blood leukocytes from rats. Further, the zerumbone treatment on the human PBMCs activated with LPS showed significant inhibition in the expression of ICAM1, COX-2, 5-LOX, and the generation of inflammatory cytokines compared to the control. Overall, the data presented infers that zerumbone positively modulates critical enzymes and receptors of eicosanoids in leukocytes activated with lipopolysaccharides. Thus, zerumbone can be a potential anti-eicosanoid drug in managing inflammation.

01 Jun 2024·CARTILAGE

Inhibition of Leukotriene A₄ Hydrolase Suppressed Cartilage Degradation and Synovial Inflammation in a Mouse Model of Experimental Osteoarthritis

Article

Author: Prasadam, Indira ; Wang, Yanping ; Crawford, Ross ; Xiao, Yin ; Sun, Antonia RuJia ; Wu, Xiaoxin ; Mao, Xinzhan

Objective Chronic inflammation plays an important role in the osteoarthritis (OA) pathology but how this influence OA disease progression is unclear. Leukotriene B4 (LTB4) is a potent proinflammatory lipid mediator generated from arachidonic acid through the sequential activities of 5-lipoxygenase, 5-lipoxygenase–activating protein, Leukotriene A4 hydrolase (LTA4H) and its downstream product LTB4. The aim of this study is to investigate the involvement and the potential therapeutic target of the LTB4 pathway in OA disease progression. Design Both clinical human cartilage samples ( n = 7) and mice experimental OA models ( n = 6) were used. The levels of LTA4H and leukotriene B4 receptor 1 were first examined using immunostaining in human OA/non-OA cartilage and mice experimental OA models. We also determined whether the LTA4H pathway was associated with cartilage degeneration and synovitis inflammation in OA mice models and human articular chondrocytes. Results We found that both LTA4H and LTB4 receptor (BLT1) were highly expressed in human and mice OA cartilage. Inhibition of LTA4H suppressed cartilage degeneration and synovitis in OA mice model. Furthermore, inhibition of LTA4H promoted cartilage regeneration by upregulating chondrogenic genes expression such as aggrecan ( ACAN), collagen 2A1 ( COL2A1), and SRY-Box transcription factor 9 ( SOX9). Conclusions Our results indicate that the LTA4H pathway is a crucial regulator of OA pathogenesis and suggest that LTA4H could be a therapeutic target in combat OA.

31 May 2024·Japanese Journal of Infectious Diseases

Dysregulated Leukotriene Metabolism in Patients with COVID-19

Article

Author: Yavuz, Hayrettin ; Pınarbaşı, Ergun ; Doğan, Halef Okan ; Sarıismailoğlu, Rağıp ; Zararsız, Gözde Ertürk ; Bolat, Serkan ; Doğan, Kübra ; Şenol, Onur ; Yerlitaş, Serra İlayda ; Budak, Mahir ; Büyüktuna, Seyit Ali

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

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