High affinity IL-2 inhibitor

"Tethering" technology yields small molecule antagonist of difficult target

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BOSTON — Scientists from Sunesis, of South San Francisco, California, reported at the 7th annual Drug Discovery Technology Conference, held here this week, that they have isolated a small molecule inhibitor of the human cytokine interleukin-2 (IL-2) using the company's "tethering" technology.

Previously, researchers had developed only protein inhibitors of IL-2, which must be injected, according to Sunesis Chief Scientific Officer and President James Wells, who said the current work demonstrates that it is possible to find small molecules that bind tightly to what some considered intractable targets.

The Sunesis technology, first reported in 2000, uses drug fragments (approximately 250 Da) rather than whole molecules as the starting point for screening. The technique allows researchers to search the equivalent of several million structures while synthesizing only several thousand compounds.

However, the binding affinity of small fragments can be low. To capture low-affinity binders, Sunesis developed the tethering technology, which creates ...

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