Subject: Re: CCL:FW: Drug-like inactive molecules

From: [email-masked]
Date: Wed, 1 Sep 1999 13:56:40 -0400 (EDT)

I think the idea is an interesting one, particularly of benefit to a
company with statistical tools to infer subsets of data that might lead to
heuristics, such as your company.

I question the value of the data in the absence of enough positives
however.  The ability to discern rules, either by decision trees or by
another qsar-like system would seem to be far less 'bounded' than one
which is driven by the actual hits.

Related then to this is the problem of relating the definition of a hit
across different screens, let alone different companies or academics.  HTS
is usually +/- and threasholds are frequently different.  In addition,
compounds that are directly assayed by one group often have activities
differing by an order of magnitude or more when assayed by another group.
There are often normalizing compounds, but sometimes not and sometimes
there is just that much noise.

Without big pharma databases to reduce the noise, I would question the
possibility of useful conclusions arising.

Is there an estimate of the number of compounds screened in strictly
non-commercial enterprises as compared with the total number of compounds
screened by the pharmaceutical companies and 'near-pharma' companies such
as startups with a special chemistry hook or even academics that have
discovered a commercial interest?

I would hazard a guess that the commercial side is on the order of 20-50M
compounds (including combi-libs actually synthesized and tested) and
academics 100K-1M.  I do not really know the number though.
__
M. Dominic Ryan   (610)-270-6529     SmithKline Beecham Pharmaceuticals 
Internet:  [email-masked]     King of Prussia, PA