Introduction:Introduction 14/1/10 20:18 Page 7
Introduction
introduction
T
here is probably no such thing as a typical edition of Drug afford the investment
Discovery World, but in this number, as we enter the second decade required but now there
of our existence, we include at least one novel contribution in the are freely accessible online
shape of a transcript of a roundtable discussion chaired by Robert Jordan, resources exemplified by
our editor-in-chief and publisher. The subject was a topical one – current and PubChem which is
emerging trends in cell-based assays. The discussion makes interesting described in an article in
reading. There appears to have been general agreement among the this number of DDW. The
participants that functional cell-based assays are likely to provide more authors caution, however,
biologically relevant data than the more traditional biochemical assays. that there are potential
There are still debates about what types of cells to use, whether whole cells risks residing in the data
or membranes should be employed, whether the functionality being including inconsistencies
measured truly mimics the disease situation being targeted, etc. In some and quality issues. They
circumstances a case can still be made for a combination of both examine what is lacking in
biochemical and cell-based assays. However, there seemed to be no serious the present resources and
disagreement with the statement made by one of the participants that “the have suggestions for
cell-based assay has probably emerged up-front now”. future approaches which
Another unusual for us, but very interesting, article discusses the growing could provide reliable
importance of Singapore as a centre for pharmaceutical and biotech internet-based resources
companies to base their regional headquarters and R&D and manufacturing for drug discovery.
facilities. It is stated that there are now more than 16,000 people employed Another article also
in more than 100 biomedical science companies and 30 research/medical points out the immensity of the task in selecting suitable molecules for
institutes on the island. Singapore is increasingly seen as a ‘strategic beach- development among the vast numbers which are theoretically available.
head site’ as companies move to gain an increasing presence in the vast and There are, it is stated, 10
60
possible small-molecule compounds in the so-
rapidly expanding Asian healthcare markets which were valued at US$240 called chemical space giving a ‘needle-in-a-haystack’ type of problem when
billion in 2008 and expected to grow by some 5-10% in 2009. The fact that seeking new therapeutic agents. High throughput screening helps as do other
Singapore only entered this sector seriously in 2000 is a tribute to its agility approaches, such as fragment-based drug design. These, and other
and willingness to set up the appropriate infrastructures to allow this techniques, are reasonably helpful in identifying compounds with potential
dramatic expansion. efficacy but much less good at predicting toxicity. Clearly any methodology
The remainder of the articles in this edition of DDW are concerned with which can detect potential toxicity at an early stage would reduce wastage
various technological innovations all, in one way or another, designed to of cash and resources. Our authors advocate the integration of
meet the relentless requirement for new, useful and profitable medicines. computational methods into the drug discovery process involving the use of
One author states that a general response he receives when discussing the a reliable in silico toxicity screening method. They discuss the advantages
state of innovation in drug discovery technology is that it has declined and limitations of such an approach.
significantly. Unfavourable comparisons are made with the consumer Design of experiments (DOE) is a well-proven statistical method which
electronics industry with its more powerful computers, more sophisticated has broad applications across many disciplines and industries. In another
cell phones and the like. Our author concludes, however, that innovation is article our author suggests that it could, with advantage, be used in assay
cyclical and that we may just be in a temporary trough, albeit a prolonged development which represents something of a bottleneck in may drug
one. We must all hope that he is right! discovery laboratories. He points out that currently only one vendor offers
The introduction of many new technologies over the past two decades or specific software for investigating DOE in biological assays and he believes
so is not without its problems. Even large pharmaceutical companies do not that a market opportunity exists for other systems which will allow the full
have the resources to invest in all these technologies and, in any event, it may potential impact of DOE on assay development to be realised.
not be the correct decision to do so. Authors from Wyeth Laboratories Regulatory authorities have recently stepped up their requirements for
describe how that company has used portfolio and project management quantitative data on the behaviour of potential new drugs and their
(PPM) tools together with scientific expertise to ensure transparency and metabolites in man. This requirement can be met by the use of carbon-14
alignment in applying technologies and to measure the return on investment labelled compounds. Very low levels of C-14 can be detected by the use of
in terms of improvements in quality of the drug discovery pipeline. The accelerator mass spectrometry (AMS) enabling low doses which pose no
approach is exemplified in respect of a newly introduced technology, an radiation risk to be administered to man. It is essential that no impurities are
establishing but still new capability and a well established and present in the labelled compounds – their presence could give rise to
organisationally mature technology platform. spurious results.
Linked to the introduction of new technologies is the issue of coping with, The consequence of this is that several custom labelling suppliers have
and generating the maximum amount of useful and relevant information invested in appropriate facilities to produce good quality C-14 labelled
from, the vast quantities of data which are generated. Over the years we compounds. Some large companies have their own facilities but others are
have carried many articles indicating the importance of informatics in this out-sourcing. Our article focuses on the new uses for C-14 compounds,
context. In one of the articles here there is discussion of ways in which discusses the factors which influence their preparation and indicates how
leveraging research informatics can lead to an acceleration in drug discovery. suppliers are responding to the increasing demand for such compounds.
The use of techniques such as combinatorial chemistry which generate
vast numbers of chemical structures has led to the development of
cheminformatics. Until relatively recently only large organisations could Dr Roger Brimblecombe PhD, DSc, FRCPath, FIBiol
Drug Discovery World Winter 2009/10 7
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