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Last update 08 May 2025

FLAP

Last update 08 May 2025

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 [+1]

Inactive Indication

Acute Coronary Syndrome [+1]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BRP-201

Target

FLAP

Mechanism

FLAP inhibitors

Active Org.

Friedrich Schiller University of Jena

Originator Org.

Friedrich Schiller University of Jena

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AZ-13581258

Target

FLAP

Mechanism

FLAP inhibitors

Active Org.

AstraZeneca PLC

Originator Org.

AstraZeneca PLC

Active Indication

Lung Diseases

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

/ TerminatedPhase 2IIT

PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression as measured on serial computer tomographic coronary angiography.

Start Date12 Jul 2021

Sponsor / Collaborator

University of Otago

[+1]

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

732

Literatures (Medical) associated with FLAP

01 Dec 2025·Inflammation Research

Histamine and TH2 cytokines regulate the biosynthesis of cysteinyl-leukotrienes and expression of their receptors in human mast cells

Article

Author: Werfel, Thomas ; Mommert, Susanne ; Schaper-Gerhardt, Katrin ; Gutzmer, Ralf ; Röhn, Till A ; Hasler, Franziska ; Gehlhaar, Patricia

AbstractIntroductionIn skin lesions of atopic dermatitis (AD), a chronic inflammatory skin disease, mast cells beyond other immune cells are present in increasing numbers. Upon activation, mast cells release a plethora of mediators, in particular histamine and leukotrienes, as well as chemokines and cytokines, which modulate the immune response of cells in their microenvironment and may influence mast cells in an autocrine loop. This study investigated the effects of histamine and TH2 cytokines on the biosynthesis of cysteinyl leukotrienes (CysLTs) as well as CysLT receptor expression on human mast cells from healthy volunteers and patients with AD.MethodsHuman mast cells were generated from CD34+ progenitor cells from peripheral blood. The cultured mast cells were stimulated with IL-4, IL-13, histamine and different histamine receptor selective ligands. Expression of enzymes in the biosynthesis of leukotrienes and expression of CysLT receptors were quantified by real-time PCR. The release of CysLTs was measured by ELISA. ResultsMast cells from AD patients showed higher expression of 5-Lipoxygenase (5-LO) and 5-Lipoxygenase activating protein (FLAP) compared to mast cells from healthy volunteers at baseline and in presence of histamine and TH2 cytokines. Expression of leukotriene C4 synthase (LTC4S), the biosynthesis of CysLTs, and mRNA expression of both CysLT receptors were induced by histamine and TH2 cytokines in mast cells from healthy volunteers and AD patients.ConclusionWe provide evidence that in an acute allergic situation histamine and TH2 cytokines may activate the biosynthesis of pro-allergic cysteinyl leukotrienes and up-regulation of CysLT receptor expression in human mast cells. This suggests a novel mechanism for sustaining mast cell activation through a possible autocrine signalling loop under these conditions.

01 Jan 2025·Current Therapeutic Research

Alpha-Lipoic Acid-Mediated Inhibition of LTB4 Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells

Article

Author: Contreras, Héctor R ; Valle, Alexandra ; Castellón, Enrique A ; López-Moncada, Fernanda ; Gv, Kevin Brockway ; Ríos, Juan Carlos ; Faúndez, Mario ; Indo, Sebastián ; Torres, María José

BackgroundLeukotriene B₄ (LTB₄) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB₄ is mediated by leukotriene A₄ hydrolase (LTA₄H), and it binds to the receptors BLT₁ and BLT₂. Dysregulation in LTB₄ production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB₄ synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTA₄H. The objective of this study was to evaluate the effect of ALA on the expression of canonical EMT markers and the functional and tumorigenic capacities induced by LTB₄ in A549 cells.MethodsThe expression of cPLA₂, 5LOX, FLAP, LTA₄H, BLT1, and LTB₄ production in human adenocarcinomic alveolar basal epithelial A549 cells was assessed using Western blot, RT-qPCR, and ELISA, respectively. Subsequently, the expression of canonical EMT markers was evaluated by Western blot. Functional assays were performed to assess cell viability, proliferation, invasion, migration, and clonogenicity using MTT, Western blot, Transwell assays, and colony formation assays, respectively. Results were expressed as median with interquartile range (n≥3) and analyzed using the Kruskal-Wallis or Tukey multiple comparisons tests.ResultsA549 cells express key proteins involved in LTB₄ synthesis and receptor binding, including LTA₄H and BLT₁, and ALA inhibits the production of LTB₄. Additionally, LTA₄H and BLT1 were detected in lung adenocarcinoma tissue samples. LTB₄ was found to induce EMT, whereas ALA treatment enhanced the expression of epithelial markers and reduced the expression of mesenchymal markers. Furthermore, ALA treatment resulted in a decrease in LTB₄ levels and attenuated the functional and tumorigenic capacities of A549 cells, including their viability, migration, invasion, and clonogenic potential.ConclusionsThese findings suggest that ALA may offer therapeutic potential in the context of lung cancer, as it could be integrated into conventional pharmacological therapies to enhance treatment efficacy and mitigate the adverse effects associated with chemotherapy. Further studies are warranted to confirm the clinical applicability of ALA as an adjunctive treatment in lung cancer.

01 Jan 2025·Archiv der Pharmazie

2‐Phenylbenzothiazoles featuring heteroaryl sulfonamide end‐capping substructures as developable mPGES‐1 inhibitors

Article

Author: Çalışkan, Burcu ; Olğaç, Abdurrahman ; Werz, Oliver ; Dahlke, Philipp ; Maz, Tuğçe Gür ; Banoglu, Erden ; Yalçın, Tansu ; Jordan, Paul M.

AbstractThe inhibition of human microsomal prostaglandin E2 (PGE2) synthase‐1 (mPGES‐1) is a promising therapeutic modality for developing next‐generation anti‐inflammatory medications. In this study, we present novel 2‐phenylbenzothiazole derivatives featuring heteroaryl sulfonamide end‐capping substructures as inhibitors of human mPGES‐1, with IC50 values in the range of 0.72–3.40 µM in a cell‐free assay of PGE2 formation. Notably, compound 21, featuring a quinoxalinedione ring in its sulfonamide segment, effectively suppresses PGE2 biosynthesis at a low micromolar concentration (IC50 = 0.72 µM) with exceptional selectivity against cyclooxygenase (COX)‐1, COX‐2, 5‐lipoxygenase (5‐LOX), and FLAP. This compound offers a novel chemical scaffold for developing safer and more effective anti‐inflammatory agents.

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