Introduction


introduction T


he first edition of Drug Discovery World appeared 10 years ago. The articles in that issue included one on High Throughput Screening (HTS) which was then seen to be ‘set to become one of the cornerstones of drug discovery’. Interestingly, the current edition also carries an article on HTS. Clearly the technology has become an integral part of the drug discovery process and our authors focus on the fact that the time taken to develop a new HTS assay has reduced significantly, especially during the last few years, and is now six months or less on average. This, they state, is due to the skill of scientists but also to the availability of precise automated instruments, and high quality compounds and reagents.


The development of HTS was accompanied by a greatly increased use of combinatorial chemistry – again discussed in our Summer 2000 edition. Since then we have carried a number of articles indicating an ever increasing tendency over the years to move on from the ‘blunderbuss’ approach of yore to more focused, dedicated compound libraries containing fewer, purer, well-profiled compounds. Inevitably, in 2000, there was much conjecture about the impact the output from the Human Genome Project would have on drug discovery and this was discussed in an article in our first edition as it has been in many subsequent articles. In the last decade genomics and proteomics have come into their own, not only in drug discovery, but also in the advances towards personalised medicine, a term not used much, if at all, 10 years ago. In the current number there is a discussion of the present market and regulatory landscape as it relates to personalised medicine which is probably most advanced in the cancer field where numbers of disease-associated biomarkers have already been identified and validated. All the indications are that there will be progression of this approach into many therapeutic areas beyond oncology. Biomarkers were not discussed 10 years ago nearly as much as they


are now. In one of the articles in this edition it is stated that the number of scientific publications relating to this subject has increased from 20,000 to 40,000 per annum over the last decade. The authors quote the NIH definition of a biomarker as ‘a characteristic objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention’. As such, biomarkers can, as indicated in the previous paragraph, serve as an indicator of specific diseases but also, in drug discovery, can play an important role in target validation, in drug candidate development and in clinical trials assessment. Cell culture has, of course, been with us for many years but the next development will, apparently, be a transition from conventional two- dimensional (2D) culture vessels to a three-dimensional (3D) environment. Structural scaffolds are being developed on which specific cell types can be cultured. This has great potential in, for example, tissue engineering research. However, in an article reviewing the current situation our author cautions that fully validated or robust 3D culture solutions are still some way off . Fluorescence lifetime (FLT) dates back nearly a decade. It was introduced in 2002 as a detection modality on a multi-mode plate reader but for various technical reasons FLT assays are not used routinely in most drug discovery laboratories. However, intrinsically such assays have many benefits. The results of a recent survey summarised in this edition of DDW have revealed ‘a latent appetite’ especially in the protease and kinase research. New developments in instrumentation are now appearing which may help to satisfy this appetite.


The use of electronic laboratory notebooks (ELNs) has increased Drug Discovery World Summer 2010


enormously during the last decade and beyond. Initially they were used essentially to replace paper-based laboratory notebooks, especially in chemistry laboratories. More recently their use has spread into the more biological disciplines of, for example, pharma- cology, drug metabolism and pharmacokinetics. Now, as pointed out and discussed in one of our articles, the time is ripe to make even more use of the ‘corporate knowledge’ captured on ELNs. This could, the


authors claim, ‘reduce the burden of regulatory compliance’ among other things.


In the last edition of DDW we carried an article giving an overview of Companion Diagnostics in the pharmaceutical industry. The message was that pharmaceutical companies will have to produce more genotype and/or phenotype-focused therapeutic agents. In a follow up article in this edition there is a discussion of the nuances and difficulties of putting together deals in the Companion Diagnostic space. The all- important question of how the regulatory agencies will deal with Companion Diagnostics is also discussed. We rarely receive articles on advances in treatments for ophthalmological diseases despite the fact that, with an ageing population, they are becoming an increasing problem. However, we carry here a review of new trends and therapeutic approaches in the management of diabetic retinopathy. It is stated that an estimated 220 million people worldwide suffer from diabetes mellitus. About 2% of people become blind after 15 years of diabetes and about 10% develop severe visual impairment. Therapeutic approaches are aimed at the various aspects of the pathophysiology of both non-proliferative and proliferative diabetic retinopathy. Anti-angiogenic and anti- inflammatory agents given either locally or systemically are being studied with promising results. To return, finally, to the Summer 2000 edition of DDW and to articles not referred to above. These included an enthusiastic view about the future for therapeutic vaccines which has probably proved to be justified. An article on plants as a source of new medicines stated that ‘in the near future we may well start to see the emergence of a new class of prescription medicine containing complex mixtures of plant extracts…’ That may still be wishful thinking. There was a prediction that there would be an increasing reliance on Contract Research Organisations (CROs) by the big pharmaceutical companies. This was a correct prediction as was the view expressed in another article that ‘the key to exploiting the riches of genomics is bioinformatics’. We look forward to the next 10 years of our journal


Dr Roger Brimblecombe PhD, DSc, FRCPath, FIBiol 7


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