MK-886
MK-886 is a drug that was initially developed as a leukotriene antagonist but was later found to have other modes of action. It is a potent and selective inhibitor of 5-lipoxygenase activating protein (FLAP), which is involved in the synthesis of leukotrienes. MK-886 also inhibits the peroxisome proliferator-activated receptor alpha (PPARα), a key regulator of lipid metabolism and inflammation.
History[edit | edit source]
MK-886 was first synthesized by Merck & Co. in the 1980s as a potential treatment for asthma and inflammatory diseases. However, clinical trials were discontinued due to the occurrence of side effects such as flu-like symptoms and elevated liver enzymes.
Mechanism of action[edit | edit source]
MK-886 inhibits the 5-lipoxygenase activating protein (FLAP), which is involved in the synthesis of leukotrienes. Leukotrienes are inflammatory mediators that can cause bronchoconstriction and increase mucus production in the lungs. By inhibiting FLAP, MK-886 reduces the production of leukotrienes, thereby potentially reducing inflammation and symptoms of asthma.
In addition to its effects on FLAP, MK-886 also inhibits the peroxisome proliferator-activated receptor alpha (PPARα). PPARα is a nuclear receptor that regulates the expression of genes involved in lipid metabolism and inflammation. Inhibition of PPARα by MK-886 may therefore have effects on lipid metabolism and inflammation.
Clinical significance[edit | edit source]
Despite the discontinuation of clinical trials, MK-886 has been widely used in preclinical research to study the role of leukotrienes and PPARα in various diseases. It has been used in studies of asthma, allergic rhinitis, atherosclerosis, cancer, and other conditions.
See also[edit | edit source]
- Leukotriene antagonist
- 5-lipoxygenase activating protein
- Peroxisome proliferator-activated receptor alpha
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