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Compound Discovered That Reverses Gene ‘Silencing’

Compound Discovered That Reverses Gene ‘Silencing’

SEATTLE—Researchers at the Fred Hutchinson Cancer Research Center have discovered a chemical compound that reverses a process called silencing, in which genes or chromosomal regions are shut off (Proc Natl Acad Sci 98:15113-15118, 2001).

The research team, working in the lab of Dan Gottschling, PhD, focused their drug search on a silencing protein called Sir2p, which has been found to modulate the function of the tumor-suppressor protein p53. Thus, drugs that inhibit Sir2p could potentially activate silenced p53 genes and prevent tumor growth.

After screening 6,000 chemical compounds, the investigators identified one that effectively blocked all of Sir2p’s silencing capabilities. Lead investigator Antonio Bedalov, MD, PhD, named the compound splitomicin after his hometown Split, Croatia.

The researchers found that the only role of splitomicin is to inhibit Sir2p function, which makes the drug highly specific to its target, an attractive feature for drug design.

"Our hope is that this chemical/genetics approach can lead to quicker development of treatments for people with cancer and other diseases," Dr. Bedalov said in a news release announcing the discovery.

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