02 March 2009

Fragments in the clinic: How many?

At the Tri-Conference last week, Maria M. Flocco of Pfizer stated that a search of the IDDB3/Prous databases yielded 30 examples of compounds that had made it into the clinic from fragment-based approaches, of which 23 are still active, and 4 are in Phase II testing.

And not just in the clinic. According to her, tipranavir, an HIV protease inhibitor approved by the FDA in 2005, was derived from a 30 micromolar hydroxycoumarin fragment, back before people really thought in terms of fragments. This leads to the question, how many approved drugs could be considered the result of fragment-based drug discovery? I have argued that sorafenib fits the bill, having started from a relatively weak (17 micromolar) fragment-like screening hit. Any others?

BTW: Readers of Practical Fragments had previously identified 17 clinical compounds discovered through fragment-based methods. You can read that discussion here.

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