Number: 2000-010-1-700
Title: Human drug metabolism database
Task Group
Chairman: Paul W.
Erhardt
Members: Gabrielle
Hawksworth (Chairperson Drug Metab. Sect. IUPHAR)
Remarks: IUPHAR/ICSU grant support
Objective:
Establish a model database for hdrug metabolism information that
can be mounted on the WEB.
Description:
Having had the privilege of interacting with over 50 international
experts in the area of drug metabolism during the course of a previous
IUPAC 18- month working party on the topic of drug
metabolism databases, then spending another 6 months interacting
with Blackwell to effect the publication of a book on the working
party's efforts and, finally, having participated in five major scientific
symposia also dealing with this theme, it has become very clear that
what the drug metabolism field needs more than anything else, is a
commonly held Human Drug Metabolism Database. This relational database
coupled with substructure searching capability should be derived solely
from in vivo, clinical results that are continually being contributed
by everyone. In turn, the database should be available to everyone
via a non-profit mechanism. Thus, the operation and utility of this
metabolism database might be imagined to be somewhat similar to that
of the Cambridge x-ray collection.
The sheer size of such a common database can overcome the anecdotal
nature of the numerous smaller collections presently being held individually
by the big pharma members of the pharmaceutical enterprise. And it
will be the database's critical mass that will allow it to be utilized
to develop more accurate and meaningful human structure-metabolism-relationships
(hSMRs). Selected aspects of the overall SMRs, in turn, could then
still be applied by individuals in a proprietary fashion to better
predict the metabolic fate of their own, specific structural motifs.
Perhaps even more important, however, is that the assembly of this
type of database may be the only way to assess and potentially validate
the actual utility of the pending explosion of biochemical and in
vitro metabolism data and techniques. The latter are already beginning
to hit the drug discovery and development arena due to the trend toward
high-throughput metabolism screening of compound libraries as well
as to the systematic exploration of in vitro SMR data associated with
the specific hCYPs (human metabolizing enzymes) that can now be readily
isolated via genetic engineering and biochemical separation.
Toward the establishment of such a database we have recently initiated
a collaboration in this area with the IUPHAR who seem equally excited
about this possibility. Importantly, this expanded relationship offers
the potential to extend beyond the big pharma's clinical data, as
typically collected in U.S. or European based trials, so as to also
include a much broader and diverse representation of ethnic genotypes
and cultural phenotypes. Thus, as the field of drug metabolism rolls
into the future, it is certain that if a commonly held, human database
can indeed be produced, the entire world should be able to benefit
from such an undertaking.
Progress:
(April 2002) A preliminary skeleton of the information
to be included in the database has been assembled and the programs
for the actual database construction are starting to be written. Programs
are being written in JAVA for use within Oracle. The latter will be
mounted on a double-server system (one for the database itself and
the other for enablement of www users) that will be fully supported
and protected by the University's Computer Informatics resource.
We hope to have a prototype
(with a limited amount of data entered) available by mid 2002 so that
it can be taken on a global road-show during the latter half of the
year and into early 2003. After refinement and finalization of the
prototype's features, mass input of human drug metabolism data will
commence.
(May 2007) A prototype of the database has been assembled
and a limited amount of data has been entered so as to allow for a
demo version. The latter revealed both construction and data-entry
flaws that need to be corrected. The revamped plan is to seek a partner
from the private sector to assist in fine-tuning the database construction
since these costs and the placement of our Oracle version in the public
domain have become prohibitive.
Last Update: 8 May 2007
<project announcement published
in Chem.
Int.
23(3) 2001>