ALOX5 binds ALOX5 inhibitors

Stable Identifier
Reaction [binding]
Homo sapiens
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Eicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth muscle contraction and relaxation, and the release of gastric acid. Eicosanoids are synthesized in humans primarily from arachidonic acid (AA) that is released from membrane phospholipids. Once released, AA can be acted on by various enzymes to form different eicosanoids. Arachidonate lipoxygenase 5 (ALOX)5 form leukotrienes (LTs) and eicosatetraenoic acids (ETEs) from AA. LTs and ETEs are biologically active molecules formed in response to inflammatory stimuli. They cause contraction of bronchial smooth muscles, stimulation of vascular permeability, and attraction and activation of leukocytes. When produced in excess, these molecules may contribute to a wide range of pathological inflammatory responses.

ALOX5 inhibitors are compounds that slow or stop the action of the ALOX5 enzyme, which is responsible for the production of inflammatory LTs and ETEs. Zileuton blocks the activity of ALOX5 (Carter et al. 1991). Zileuton is used in the treatment of acne vulgaris (Zouboulis 2005, Zouboulis et al. 2009) and for the prophylaxis and chronic treatment of allergic asthma (Bruno et al. 2018, Morina et al. 2016). Meclofenamic acid is a non-steroidal anti-inflammatory drug (NSAID) used for the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss. It is also used for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis. In vitro meclofenamic acid was found to be an inhibitor of human ALOX5 activity (Boctor et al. 1986). Balsalazide, olsalazine and sulfasalazine are all pro-drugs that are enzymatically cleaved in the colon to produce the anti-inflammatory agent mesalazine (5-aminosalicylic acid, 5-ASA, mesalazine (Klotz 1985, Selby et al. 1985, Sharon et al. 1978, Hawkey et al. 1985, Neilsen et al. 1987). Once metabolised, 5-ASA acts locally in the colon to reduce inflammation in conditions such as inflammatory bowel disease and ulcerative colitis (Wiggins & Rajapakse 2009, Rask-Madsen et al. 1992, Singer et al. 2006, Hoult 1986, Feagan & Macdonald 2012).

Literature References
PubMed ID Title Journal Year
29133059 Recent advances in the search for novel 5-lipoxygenase inhibitors for the treatment of asthma

Spaziano, G, Nabavi, SM, D'Agostino, B, Sureda, A, Liparulo, A, Filosa, R, Roviezzo, F, Bruno, F

Eur J Med Chem 2018
30669 Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine

Sharon, P, Zor, U, Rachmilewitz, D, Ligumsky, M

Gastroenterology 1978
16795963 Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis--results of a field study

Schmausser, H, Singer, MV, Schönfeld, G

Hepatogastroenterology 2006
3933675 Olsalazine in active ulcerative colitis

Jewell, DP, Mason, CH, Ireland, A, Barr, GD, Selby, WS

Br Med J (Clin Res Ed) 1985
2866075 Modulation of human colonic arachidonic acid metabolism by sulfasalazine

Hawkey, CJ, Boughton-Smith, NK, Whittle, BJ

Dig Dis Sci 1985
2877850 Pharmacological and biochemical actions of sulphasalazine

Hoult, JR

Drugs 1986
19743890 Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis

Rajapakse, R, Wiggins, JB

Expert Opin Drug Metab Toxicol 2009
2882965 Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid

Elmgreen, J, Bukhave, K, Nielsen, OH, Ahnfelt-Rønne, I

Dig Dis Sci 1987
3020588 Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro

Boctor, AM, Pugsley, TA, Eickholt, M

Prostaglandins Leukot Med 1986
20436887 Zileuton, a new efficient and safe systemic anti-acne drug

Zouboulis, CC

Dermatoendocrinol 2009
27046942 Maximum Time of the Effect of Antileukotriene - Zileuton in Treatment of Patients with Bronchial Asthma

Morina, N, Iljazi, A, Boçari, G, Hyseini, K, Halac, G

Acta Inform Med 2016
1848634 5-lipoxygenase inhibitory activity of zileuton

Brooks, DW, Bell, RL, Bouska, J, Summers, JB, Young, PR, Dyer, R, Albert, DH, Carter, GW

J Pharmacol Exp Ther 1991
1359745 5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease

Bukhave, K, Laursen, LS, Rask-Madsen, J, Lauritsen, K

Agents Actions 1992
15604543 Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production

Zouboulis, ChC, Saborowski, A, Boschnakow, A

Dermatology 2005
2864155 Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid

Klotz, U

Clin Pharmacokinet 1985
23076889 Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis

Macdonald, JK, Feagan, BG

Cochrane Database Syst Rev 2012
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