The Failure of Target-Oriented Drug Discovery

There is a fascinating case history of the development of five drugs in the current Nature Drug Discovery. Among other things, it concludes that target-oriented drug discovery isn’t working as well as its promoters say. It has partly to do with the notion of magic bullets and exclusivity — most molecules interact with multiple targets — as well as the desirability of exclusivity itself, where compounds that interact with a few selected targets are often more desirable anyway (i.e., in cancer).

As an aside, I love drug names. They all sound like minor devils from The Omen VIII: matinib, natalizumab, bevacizumab, rofecoxib and natalizumab.


  1. Can’t forget my favourite name from biotech – a protein referred to as Diablo/Smac .
    The devil does drugs kiddies! 8p

  2. There are 2 interesting things about the generic drug names.
    1) Although they look like random attempts at high word scores in scrabble, there is actually a (semi)formal nomenclature system. Check out for a pretty good summary.
    2) Even within the confines of that nomenclature, the drug company that discovers the compound has some latitude in naming and adding prefixes and suffixes. And those choices are NOT random. A CEO of one of the world’s largest biotech companies once told me what happens. They invent a drug, and *deliberately* juxtapose difficult-to-pronounce syllables and sounds, trying to make the generic name as ugly and unpronounceable as possible.
    There is a reason for that – if the drug ever gets approved and becomes a blockbuster, it has only a finite period of market exclusivity. After a period of time (which varies) generic competitors can come into the market and significantly impair the profitability of the original drug. But that generic MUST be sold under the generic name, while the original (and only the original) gets to use the brand name.
    If given a choice between ordering 20 tablets of Exubera or 20 tabs of sildenafilozole tartrate — which do you think sounds like it will be more fun?
    Yes, the generics win business because they are the IDENTICAL compound and much cheaper – but the original brand always keeps a surprisingly high market share and higher price – and the generic nomenclature system is part of the reason why.