5-LOX activating protein

Home
Ligands
5-LOX activating protein (Human)

GtoPdb Ligand ID: 5183

Abbreviated name: FLAP

Synonyms: 5-lipoxygenase-activating protein | arachidonate 5-lipoxygenase-activating protein

Compound class: Endogenous peptide in human, mouse or rat

Comment: FLAP is a scaffolding protein involved in leukotriene (eicosanoid proinflammatory mediator) biosynthesis. It has been investigated as a molecular target for novel anti-inflammatory drugs [3,5], in particular for airway inflammation [4,6].

Species: Human

References
1. Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerstmeier J, Liening S, Werner M et al.. (2017) Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase. Sci Rep, 7 (1): 9398. [PMID:28839250]
2. Pettersen D, Broddefalk J, Emtenäs H, Hayes MA, Lemurell M, Swanson M, Ulander J, Whatling C, Amilon C, Ericsson H et al.. (2019) Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease. J Med Chem, 62 (9): 4312-4324. [PMID:30869888]
3. Pettersen D, Davidsson Ö, Whatling C. (2015) Recent advances for FLAP inhibitors. Bioorg Med Chem Lett, 25 (13): 2607-12. [PMID:26004579]
4. Pyasi K, Tufvesson E, Moitra S. (2016) Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits 'losing in translation'?. Pulm Pharmacol Ther, 41: 52-59. [PMID:27651322]
5. Sampson AP. (2009) FLAP inhibitors for the treatment of inflammatory diseases. Curr Opin Investig Drugs, 10 (11): 1163-72. [PMID:19876784]
6. Stevens WH, Lane CG, Woolley MJ, Ellis R, Tagari P, Black C, Ford-Hutchinson A, O'Byrne PM. (1994) Effect of FLAP antagonist MK-0591 on leukotriene production and ozone-induced airway responses in dogs. J Appl Physiol, 76 (4): 1583-8. [PMID:8045835]
7. Takahashi H, Riether D, Bartolozzi A, Bosanac T, Berger V, Binetti R, Broadwater J, Chen Z, Crux R, De Lombaert S et al.. (2015) Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915). J Med Chem, 58 (4): 1669-90. [PMID:25671290]

References

1. Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerstmeier J, Liening S, Werner M et al.. (2017)
Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase.
Sci Rep, 7 (1): 9398. [PMID:28839250]

2. Pettersen D, Broddefalk J, Emtenäs H, Hayes MA, Lemurell M, Swanson M, Ulander J, Whatling C, Amilon C, Ericsson H et al.. (2019)
Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease.
J Med Chem, 62 (9): 4312-4324. [PMID:30869888]

3. Pettersen D, Davidsson Ö, Whatling C. (2015)
Recent advances for FLAP inhibitors.
Bioorg Med Chem Lett, 25 (13): 2607-12. [PMID:26004579]

4. Pyasi K, Tufvesson E, Moitra S. (2016)
Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits 'losing in translation'?.
Pulm Pharmacol Ther, 41: 52-59. [PMID:27651322]

5. Sampson AP. (2009)
FLAP inhibitors for the treatment of inflammatory diseases.
Curr Opin Investig Drugs, 10 (11): 1163-72. [PMID:19876784]

6. Stevens WH, Lane CG, Woolley MJ, Ellis R, Tagari P, Black C, Ford-Hutchinson A, O'Byrne PM. (1994)
Effect of FLAP antagonist MK-0591 on leukotriene production and ozone-induced airway responses in dogs.
J Appl Physiol, 76 (4): 1583-8. [PMID:8045835]

7. Takahashi H, Riether D, Bartolozzi A, Bosanac T, Berger V, Binetti R, Broadwater J, Chen Z, Crux R, De Lombaert S et al.. (2015)
Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915).
J Med Chem, 58 (4): 1669-90. [PMID:25671290]