[QSAR] Structural alerts for endocrine disruptors

[List for Members of Cheminformatics and QSAR Society]

Monika,

        You should consider QSAR models for various endocrine activities 
in 
your review.

        Pipeline Pilot has very good software tools for constructing and 
analyzing
Bayesian models from activity data for a variety of chemotypes.   The 
resulting models 
include probabilities that certain structural fragments will be associated 
with particular
biological activities.  The probabilities for the fragments are then added 
up for the
entire molecule resulting in a Bayesian score.  The fragment probabilities 
can  be 
sorted and presented as a lookup table which can aid chemists concerning 
"hot"
and "cold" spots.
 
        Earlier this year, my colleagues and I published a Bayesian model 
for the 
reactivity of small molecules towards protein thiol groups.  As 
supplemental
material, we included a table of structural fragments and probabilities. 
Although you may
not be interested in thiol reactivity, the approach used in our research 
could nonetheless 
be applied to various endocrine activities as well.  Here is the PubMed 
reference.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17340041&dopt=AbstractPlus

        For the particular case of  estrogen receptor antagonists,  I find 
it interesting that some stilbene 
analogues, which do not superficially resemble steroids (at least to my 
eye!) have endocrine activity.  Hence
these interesting bioisosteric relationships should be described in your 
review to alert readers that there
are molecules which do not necessarily "look like" steroids, yet have 
steroid-like activity.

        Regards,
        Jim Metz
 

James T. Metz, Ph.D.
Research Investigator Chemist

GPRD R46Y AP10-LL04H
Abbott Laboratories
100 Abbott Park Road
Abbott Park, IL  60064-6100
U.S.A.

Office (847) 936 - 0441
FAX    (847) 935 - 0548

james.metz at abbott.com

This communication may contain information that is legally privileged, 
confidential, or exempt from disclosure.  If you are not the intended 
recipient, please note that any dissemination, distribution, use, or 
copying of this communication is strictly prohibited.  Anyone who receives 
this message in error should notify the sender immediately by telephone 
(847 - 936 - 0441) or return email and delete it from his or her computer.



List for Members of Cheminformatics and QSAR Society 
<qsar_society at ccl.net> 
Sent by: qsar_society-bounces at ccl.net
09/11/2007 03:09 AM
Please respond to
List for Members of Cheminformatics and QSAR Society 
<qsar_society at ccl.net>


To
<qsar_society at qsar.org>
cc

Subject
[QSAR] Structural alerts for endocrine disruptors






Dear colleagues,

currently, I am about to compile a review for the German Environmental 
Agency (UBA) about structural features that are suitable to help identify 
candidate chemicals that may have endocrine disrupting activities. 
To cover established as well as most recent research, I would appreciate 
very much if you could provide me with information (reprints, reports, 
etc.) about your work in this field. Any indications about other relevant 
work are also very welcome.

Thank you very much in advance!

Yours sincerely,

Monika Nendza
________________________
Dr. Monika Nendza
Analytisches Laboratorium
Bahnhofstr. 1
24816 Luhnstedt
Germany
T +49 4875 388
F +49 4875 585
E AL-Luhnstedt at t-online.de 


_______________________________________________
QSAR_Society mailing list
QSAR_Society at qsar.org
http://server.ccl.net/mailman/listinfo/qsar_society

-------------- next part --------------
An HTML attachment was scrubbed...
URL: http://server.ccl.net/pipermail/qsar_society/attachments/20070911/ed724a60/attachment.html