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FLAP (Arachidonate 5-lipoxygenase-activating protein) is a protein that in humans is encoded by the ALOX5AP gene. FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes. It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. Gene polymorphisms in FLAP are suspected of playing a role in Alzheimer's disease. Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory diseases. Animal and human genetic evidence suggests they may also have an important role in atherosclerosis, myocardial infarction, and stroke. The structure of FLAP provides a tool for the development of novel therapies for respiratory and cardiovascular diseases and for the design of focused experiments to probe the cell biology of FLAP and its role in leukotriene biosynthesis.

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AZD5718 (AZD-5718, AZD 5718) is a novel potent 5-lipoxygenase activating protein (FLAP) inhibitor with binding IC50 of 6.3 nM; exhibits LTB4 inhibition in human whole blood assays with IC50 of 39 nM; reduce the production of pro-inflammatory and vasoactive leukotrienes both in vitro and in vivo.




ABT-080 is a potent FLAP inhibitor that inhibits ionophore-stimulated LTB(4) formation with with IC50 of 20 nM; selectively inhibits zymosan-stimulated mouse peritoneal macrophages producing LTC(4) with IC50 of 0.16 nM, 9000-fold selectivity over PGE(2) producing; demonstrates leukotriene inhibition with oral dosing in a rat pleural inflammation model.


GSK2190915 sodium


GSK2190915 sodium is a potent, selective FLAP inhibitor with binding IC50 of 2.6 nM; inhibits LTB4 synthesis following ionophore challenge in human whole blood with IC50 of 76 nM (5 h incubation); shows good selectivity over CYP3A4, 2C9, and 2D6; exhibits excellent preclinical toxicology, pharmacokinetics and oral bioactivity.




A potent, specific and orally active 5-Lipoxygenase-activating protein (FLAP) inhibitor with IC50 of 1.6 nM in FLAP binding assay; has no inhibitory effect on 15-lipoxygenase and platelet 12-lipoxygenase and cyclooxygenase in human PMNLs; potently inhibits leukotriene (LT) biosynthesis in intact human and elicited rat PMNLs with IC50 of 3.1 and 6.1 nM, respectively; inhibits excretion of LTE4 in antigen-challenged allergic animal models.

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