The Undruggables

By Megan Scudellari The Undruggables Can young biotechs chasing elusive drug targets succeed where so many have failed? They think so. G-protein coupled receptors in the cell membrane Courtesy of Anchor Therapeutics and Arkitek Studios John Andrews finished his presentation and turned to the roomful of pharmaceutical employees. Chief scientific officer for NeurAxon, a small Canadian biotech developing pain therapeutics, Andrews braced himself for the o

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John Andrews finished his presentation and turned to the roomful of pharmaceutical employees. Chief scientific officer for NeurAxon, a small Canadian biotech developing pain therapeutics, Andrews braced himself for the onslaught. The comments came rapid-fire: Can it be produced efficiently? Yes, in just a few steps. It is really soluble? It has been from day one. Is it truly selective? Yes.

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There are many undruggable targets with enormous therapeutic and economic potential that have rankled even the best-funded laboratories over the years. Their names—Bcl-2, Ras, beta-catenin, p53, Mcl-1—are enough to induce a glassy-eyed look from scientists and a skeptical grunt from pharma executives and investors.

“The word ‘undruggable’ is a profoundly important one because it has a powerful psychological effect,” said Stuart Schreiber, director of the Chemical Biology Program at the Broad Institute in Cambridge, Massachusetts, in a 2009 news article on the Institute’s Web site.2 “It limits what ...

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