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Potent small molecule xanthine oxidase inhibitors for the treatment of gout/hyperuricemia

技术应用

- Compared to currently approved drugs, DHNB is a safe, effective, and stable XO inhibitor with similar potency as current therapies used to reduce uric acid production, but with much lower toxicity. Therefore, it is suitable for long term use to treat and/or prevent hyperuricemia and gout.- DHNB binds to the XO enzyme with high specificity. It may be used alone or in combination with traditional drugs to enhance efficacy and prevent drug resistance.- DHNB, but not other XO inhibitors, has beneficial antioxidant properties.- BCM researchers have developed novel small molecule XO inhibitors based on the chemical structure of DHNB.

详细技术说明

None

*Abstract

Gout is caused by hyperuricemia (abnormally high levels of uric acid in the blood). Approximately 4% of adults in the US (8.3 million) suffer from gout and a much larger US adult population (more than 21%) is affected by hyperuricemia. Besides gout, hyperuricemia may also lead to other severe disorders, such as renal dysfunction, metabolic syndrome, and cardiovascular diseases. Xanthine oxidase (XO) is the key enzyme in the production of uric acid and it is considered to be the most promising drug target for hyperuricemia and gout. Currently, two uric acid lowering drugs (XO inhibitors), allopurinol and febuxostat, have been used clinically to treat gout. However, both drugs may cause various and severe side effects, including life-threatening dermatological complications, and congenital malformations when used during pregnancy. Therefore, novel, safe and effective XO inhibitors are needed for hyperuricemia and gout treatment.Researchers at Baylor College of Medicine (BCM) found that a natural substance derived small molecule, DHNB, is a potent XO inhibitor. It has a different structure compared to allopurinol but demonstrates the same XO inhibitory potency both in vitro and in vivo. Further study revealed that DHNB reacts with the molybdenum center of XO enzyme with a high level of specificity, thereby blocking the conversion of xanthine to uric acid. Animal toxicity studies have shown that, at the same dosage, DHNB is free of all the toxic effects caused by allopurinol, including mortality, skin abnormality, and defects that continue into the next generation. In addition, unlike allopurinol, DHNB has antioxidant activities that can directly scavenge free radicals.

国家/地区

美国