AsianScientist (Oct. 29, 2014) – Researchers have identified several potent inhibitors that selectively target a gene associated with obesity and fat mass. These specific inhibitors could the way for the development of novel anti-obesity drugs and treatments. The findings have been published in Chemical Science.
Obesity is not merely a cosmetic problem; it predisposes the individuals to medical conditions such as Type 2 diabetes, cardiovascular diseases and certain cancers. It is estimated that by 2030, about more than half of the world’s population will be obese.
A gene known as FTO has been strongly linked to obesity, with genome studies showing that people with certain variations of the FTO gene are 70 percent more likely to become obese. This has been shown for both children and adults, as well as across all major ethnic groups, including Chinese, Malay and Indian populations in Singapore.
Identifying the FTO gene as a potential drug target, a research team led by Assistant Professor Esther Woon from the National University of Singapore looked into developing molecules that would inhibit the gene’s actions. They used a strategy combining the permutation power of dynamic combinatorial chemistry and the sensitivity of protein mass-spectrometry.
“Such remarkable selectivity is rarely achieved and is the ‘holy grail’ in drug discovery, as it potentially translates to significantly reduced side effects. This is demonstrated by the promising activities and low cytotoxicity of some of these inhibitors in cells,” said Prof. Woon.
The study authors hope that their findings will open doors for the development of novel anti-obesity drugs and treatments. They are currently working to study the molecular mechanisms and effects of the FTO inhibitors on other closely-related metabolic diseases, such as diabetes. They have filed a patent for the inhibitors.
“Recognizing a genetic, or even epigenetic, component in obesity certainly changes the way in which we approach to the treatment of the disease. What is so exciting about these FTO inhibitors is that they represent a potential new class of anti-obesity drugs, which target one of the most common genetic causes of obesity,” said Prof. Woon.
“There is still a lot to learn about the actual mechanistic link between FTO and obesity. The challenge now is to uncover the mystery through the use of these selective FTO inhibitors,” she added.
The full article can be found at: Toh et al. (2014) A Strategy Based on Nucleotide Specificity Leads to Selective Inhibition of N6-Methyladenosine Demethylase FTO.
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Source: National University of Singapore; Photo: Tony Alter/Flickr/CC.
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