Synonyms: compound 12 [PMID: 30869888]
Compound class:
Synthetic organic
Comment: AZD5718 is an inhibitor of 5-LOX activating protein (FLAP) that was developed by Astra Zeneca [4]. It is orally active and is suitable for once-daily dosing. Initial clinical findings from a first-in-human study confirmed AZD5718 target engagement, and indicated that the compound is safe and well tolerated [2]. It is being advanced for further evaluation in patients with coronary artery disease. The 5-LOX pathway has been targeted for drug development as an intervention in a number of diseases where chronic inflammation drives the pathophysiology (e.g. asthma, chronic obstructive pulmonary disease and atherosclerotic coronary artery disease). Since FLAP is a crucial regulator of 5-LOX activity, it too is being pursued as a druggable anti-inflammatory target. FLAP inhibitors and 5-LOX inhibitors reduce production of the leukotriene precursor LTA4 [1,3].
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References |
1. Bruno F, Spaziano G, Liparulo A, Roviezzo F, Nabavi SM, Sureda A, Filosa R, D'Agostino B. (2018)
Recent advances in the search for novel 5-lipoxygenase inhibitors for the treatment of asthma. Eur J Med Chem, 153: 65-72. DOI: 10.1016/j.ejmech.2017.10.020 [PMID:29133059] |
2. Ericsson H, Nelander K, Lagerstrom-Fermer M, Balendran C, Bhat M, Chialda L, Gan LM, Heijer M, Kjaer M, Lambert J et al.. (2018)
Initial Clinical Experience with AZD5718, a Novel Once Daily Oral 5-Lipoxygenase Activating Protein Inhibitor. Clin Transl Sci, 11 (3): 330-338. [PMID:29517132] |
3. Hu C, Ma S. (2018)
Recent development of lipoxygenase inhibitors as anti-inflammatory agents. Medchemcomm, 9 (2): 212-225. [PMID:30108915] |
4. 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] |