On Wed, Jan 10, 2007 at 03:35:38PM +0530, Aditya Kapil wrote: > But don't most pharma companies now use rational drug design based on > crystal structures. I realise that RDD is not perfect and will probably not
Most pharma companies do many things, rational design included. Most pharma companies are also in dire straits, because they can't match the rate of getting drugs to markets in order to remain in positive cash-flow long-term. The bottleneck are typically later stages, most very promising leads wind up duds in animal, or even human testing. > replace wet-lab efforts but aren't IT algorithms getting better. Computational drug design suffered a huge backlash after overpromising and hugely underdelivering. Ditto happened to virtual screening, and even to real high-diversity synthetic libraries. Basically, you have to have force fields good enough and fast enough so that you could model anything happening in vivo very exactly. We can't do that, in fact, we can't even fold proteins in machina properly. This is not a natural law, and will be fixed at some point. But that requires huge R&D, and the field isn't all that attractive to warrant that expediture. > 5-6 years ago there were about 500 crystal structures available after > decades of study but within the last few years this number has risen 10 > fold. Why is this? Because robotics has entered structure resolution, which hitherto was manual (black) art. > Also most libraries (combinatorial or otherwise) are against 'older' drug > targets that are functionally validated but not necessarily best in terms of > safety or efficacy profiles. Will the newer, subtler targets being > discovered now not necessitate structurally diverse classes of inhibitors? If you have your ion channel overexpressed, and can screen your libraries against it in person, this is way more worth than having a structure, even a very good structure. > Adit. > > On 1/10/07, Eugen Leitl <[EMAIL PROTECTED]> wrote: > > > > > >Actually, typically having even a very good crystal structure doesn't > >buy you all that much. Most good drugs these days come from library > >screens, and typically, they're good libraries to start with. > > > > > >This has been mentioned already, and has generated some excitement. > > > > -- Eugen* Leitl <a href="http://leitl.org";>leitl</a> http://leitl.org ______________________________________________________________ ICBM: 48.07100, 11.36820 http://www.ativel.com 8B29F6BE: 099D 78BA 2FD3 B014 B08A 7779 75B0 2443 8B29 F6BE
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