Subject: Drug-like inactive molecules

From: Roger Lahana <[email-masked]>
Date: Tue, 31 Aug 1999 18:07:54 +0200

Dear colleagues,

We are willing to assemble a database of drug-like molecules which have
been shown experimentally to be inactive against a given type of target.

By inactive, we mean that such molecules have been tested against a
certain target and measured as significantly less active (preferably 2
logs
lower) than what would be considered to be a 'hit'. All types of
receptors
are of interest.

Actually, we could well nickname such a database the World Non-Drug
Index, although we do not intend to use such a nickname for obvious
copyright infringement reasons (we are very respectful of the work done
at Derwent to maintain the World Drug Index). And, again, the
molecules we are looking for should be drug-like.

The purpose of such a database would be to have a reference data set
of inactive compounds, so as to be able to compare them with the
corresponding active molecules for any given receptor. Our intent is to
make such a database publicly available, provided that the inactive data

are sent to us on a non confidential basis. If you prefer however to
transmit us data on a confidential basis, please contact us to discuss
possible arrangements.

Thank you for your collaboration.

****************************************************************
Dr Roger Lahana                                          Synt:em
Vice-President R&D                     Parc Scientifique G.Besse
Computational Drug Discovery                         30000 Nimes
email: [email-masked]                            France
Tel: +33 (0)466 048 666                  Fax: +33 (0)466 048 667
****************************************************************
                   http://www.syntem.com
****************************************************************

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From: "Sherborne, Brad {DISC~Welwyn}" <[email-masked]>
Date: Wed, 01 Sep 1999 13:06:13 +0200

I hope that this advances debate!

Would it be more sensible for Roger's purpose to strive for SETS of
compounds that span >= 2 log units (activity and inactivity).  There are too
many compounds that are inactive against a particular target (shades of the
diversity debate here), as anyone working in industry can testify.  SETS are
obviously then up for discussion, but I'd apply a general classifier of
chemically congeneric.  These would then likely be covered in the same
patent, where such data is sometimes available.

Personally I'd see a greater importance in a "Non-drug Index" database for
focussing on congeneric sets of compounds that span bioavailable and
non-bioavailable, adverse effects and safe, etc.  I'm not sure whether this
data would be covered to any extent in public literature.

All the best

Brad
> Brad Sherborne	Registered address
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