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UCI researchers find sea anemone venom-derived compound effective in anti-obesity studies
Date:5/27/2013

Irvine, CA & Seattle, WA Scientists at UC Irvine reported this week that a synthetic compound ShK-186, originally derived from a sea anemone toxin, has been found to enhance metabolic activity and shows potential as a treatment for obesity and insulin resistance.

The findings published the week of May 27 in the Proceedings of the National Academy of Sciences reveal that ShK-186 selectively blocks the activity of a protein that promotes inflammation through the Kv1.3 potassium channel. The study presents the first evidence that the drug candidate which in March showed positive results in a Phase 1 safety clinical trial may also work in an anti-obesity capacity.

UC Irvine licensed ShK-186 to Kineta Inc., a Seattle based biotechnology company in 2009; it is the company's lead drug candidate. Kineta is developing this compound to treat autoimmune diseases, such as multiple sclerosis, psoriatic arthritis and lupus. It has also licensed the use of ShK-186 for the treatment of metabolic syndrome and obesity.

Potassium channels regulate cell membrane potential and control a variety of cellular processes. Earlier studies using mice that lack Kv1.3, a potassium channel gene, suggested that Kv1.3 regulated body weight and the basal metabolic rate.

In the present study, Dr. George Chandy and his colleagues evaluated ShK-186 because it has high selectivity for the Kv1.3 target, a favorable pharmacokinetic profile, and meets the qualities of an industry-standard drug. In tests on obese mice that ate a high-fat, high-sugar diet, ShK-186 therapy reduced weight gain, white fat deposits, fatty liver, blood cholesterol and blood sugar by activating calorie-burning brown fat, suppressing inflammation of white fat and augmenting liver function. The compound had no effect on mice that ate a standard chow diet, suggesting that the obesity-causing diet triggers the expression of the Kv1.3 target.

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Contact: Tom Vasich
tmvasich@uci.edu
949-824-6455
University of California - Irvine
Source:Eurekalert

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