Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma. Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton is marketed under the trade name ZYFLO.

Mesalamine, also known as Mesalazine or 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative colitis. Mesalazine is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects. As a derivative of salicylic acid, 5-ASA is also an antioxidant that traps free radicals, which are potentially damaging by-products of metabolism. Although the mechanism of action of mesalazine is not fully understood, it appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon. Mesalazine is used for the treatment of active ulcerative proctitis.

Meclofenamic acid, used as Meclofenamate sodium, is a non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. Meclofenamate sodium capsules are indicated for the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss; for relief of signs and symptoms of juvenile arthritis; so as for relief of the signs and symptoms of rheumatoid arthritis; For relief of the signs and symptoms of osteoarthritis. The mode of action, like that of other nonsteroidal anti-inflammatory agents, is not known. Therapeutic action does not result from pituitary-adrenal stimulation. In animal studies, meclofenamate sodium was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro, meclofenamate sodium was found to be an inhibitor of human leukocyte 5-lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamate sodium. There is no evidence that meclofenamate sodium alters the course of the underlying disease.

Sulfasalazine is an anti-inflammatory indicated for the treatment of ulcerative colitis and rheumatoid arthritis. The mode of action of Sulfasalazine or its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation, but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and in vitromodels, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of Sulfasalazine, SP and 5-ASA have indicated that the major therapeutic action may reside in the 5-ASA moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown. Sulfasalazine is used for the treatment of Crohn's disease and rheumatoid arthritis as a second-line agent. Sulfasalazine is marketed under the trade name Azulfidine among others.

Silicristin is a flavonolignan isolated from Silybum marianum and has been shown to exhibit inhibitory activities against lipoxygenase and prostaglandin synthetase. It has a role as a radical scavenger, a lipoxygenase inhibitor, a prostaglandin antagonist and a metabolite. It is a flavonolignan, a member of 1-benzofurans, a polyphenol, an aromatic ether and a secondary alpha-hydroxy ketone. Silicristin is a potent inhibitor of the thyroid hormone transporter MCT8. Silicristin is a sodium pump inhibitor, it inhibited Na(+)/K(+)-ATPase (NKA) with IC50 of 110 uM. Silicristin exhibits relatively good antioxidant effectiveness against phenylglyoxylic ketyl radicals and DPPH. Silicristin protects cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency.

PF-4191834 is a noniron chelating, non-redox inhibitor of the 5-lipoxygenase enzyme (5-LOX) that is being developed as an oral anti-inflammatory therapy for the treatment of asthma. Enzyme assay results demonstrate that PF-4191834 has an improved potency compared with its predecessor CJ-13610 and of zileuton. It was able to reduce pain and inflammation in an adjuvant-induced arthritis model in rats. PF-4191834 offers the potential to test the hypothesis that chronic inhibition of the 5-LOX enzyme will provide maximal efficacy for this target in inflammatory diseases such as asthma, chronic obstructive pulmonary disease, pain, and perhaps lupus. PF-4191834 had been in phase II clinical trial for the treatment of pain. Development was terminated in March 2011.

Darbufelone mesylate is a dual inhibitor of cellular prostaglandin and leukotriene production. Darbufelone potently inhibits PGHS-2 (IC50 = 0.19 uM) but is much less potent with PGHS-1 (IC50= 20 uM). Darbufelone is a dual inhibitor of cellular PGF2R and LTB4 production. Darbufelone is orally active and nonulcerogenic in animal models of inflammation and arthritis. Darbufelone mesylate was in phase III clinical trials by Pfizer and Zhuhai United Laboratories for the treatment of rheumatoid arthritis.

Tioxaprofen is a sulfidopeptide leukotriene receptor antagonist. It is an orally bioavailable anti-inflammatory agent, originated by Kyorin Pharmaceutical, which is being developed in clinical trials by the US company MediciNova for the treatment of interstitial cystitis and asthma. The actions of the drug are described by MediciNova as consisting of eosinophil migration inhibition, leukotriene antagonism, and phosphodiesterase IV inhibition. Other mechanisms described for Tioxaprofen include the inhibition of phosphodiesterases III, 5-lipoxygenase, phospholipase C as well as thromboxane A2. Tioxaprofen in doses of 1 and 5 mg/kg inhibits bronchoconstriction induced by inhalation of antigen and propranolol in a dose-dependent manner. Tioxaprofen was in phase III clinical trial for the treatment of asthma. However, this development was discontinued. It is under investigation for the treatment of idiopathic pulmonary fibrosis and Non-alcoholic steatohepatitis.

Piriprost (U-60, 257) is a structural analog of prostaglandin I2 (PGI2) with low IP receptor-mediated activity. It inhibits 5-LO (5-lipoxygenase). Piriprost inhibits the release of histamine and leukotrienes, implicating its role in inflammation and allergic responses. However, it was shown, that piriprost did not influence the airway responses after allergen in asthma. Nevertheless, even more, the drug was irritant to the respiratory tract than was placebo.

Licofelone (ML 3000) is a pyrrolizine derivative originally discovered by Merckle GmbH and developed by EuroAllaince with a unique pharmacological profile, which comprises optimal gastrointestinal tolerability and high analgesic and anti-inflammatory activity. These effects are due to balanced and selective inhibition of both cyclo-oxygenase and 5-lipoxygenase. Inhibition of 5-lipoxygenase may reduce the gastrointestinal toxicity associated with other non steroidal anti-inflammatory drugs, which only inhibit cyclooxygenase. Licofelone also has antipyretic and antiaggregatory properties. Clinical and preclinical trials were also undertaken for osteoarthritis, rheumatoid arthritis, asthma, pain and inflammation. However, development for these indications appear to have been discontinued.