《Pharmaceutical Bioassays-Methods and Application》，WILEY
The availability of robust bioassays is of central importance for the drug discovery process. This has been highlighted, once again very recently, by the controversy surrounding the bioactivity and therapeutic potential of “sirtuin activators”, such as resveratrol.[1–3] For some time these molecules had been regarded as promising candidates for the treatment of diabetes and various other age-related conditions, based on their ability to activate a class of NAD-dependent histone deacetylases called sirtuins.[1] However, two recent studies suggest that the “sirtuin-activating activity” of this compound class may be an artefact of the original bioassay, and that these molecules re possibly neither sirtuin activators nor promising development candidates.[2, 3] Against this backdrop, what better time than now for a systematic review and, perhaps, a critical appraisal of commonly used bioassays in drug discovery!
Does “Pharmaceutical Bioassays–Methods & Applications” deliver on these counts? The authors certainly provide a comprehensive overview of currently available assays for the screening and biological evaluation of bioactive molecules. The breadth of assay formats covered in the book is impressive, ranging from biochemical assays (e.g., for M. tuberculosis DNA polymerase b lyase, the COX and LOX enzymes etc.) through cell-based formats (e.g. , human wholeblood IFN-g assays for the screening of immunomodulators) to animal models (e.g., rat hot-plate assays), and spanning 21 different therapeutic areas from cancer to diabetes.
Interestingly, the material is organised by therapeutic area rather than methodology or assay principle. This approach has obvious dvantages for those readers interested in a particular pharmacological area, but provides very little context for the specific methodology used in individual assays. Thus, it is left to the reader, at least in the case of assay formats that have found application in different therapeutic areas, to join the dots and bring together information from various chapters. This task is not always made easier by an occasionally incomplete index. For example, the Alamar Blue assay format is a common cytotoxicity assay that has been used, with different cell types, for the screening of, for example, antibacterial and antiparasitic drug candidates. One such application is described in Chapter 3 (“Antitubercular Assays”), however, this is not cross-referenced in the index under “Alamar Blue”. The entry “Alamar Blue” in the index, on the other hand, only refers to an E. coli microplate redox assay in Chapter 16. The rather common application of Alamar Blue in antiparasitic assays is omitted altogether. Thus, it is very difficult for the reader to appreciate just how popular this reagent/assay format is for cytotoxicity studies.
The ambition of the authors to cover such an enormous range of assay formats and therapeutic areas necessarily limits the detail in which individual assays are presented. Thus, this book is essentially a comprehensive collection of assay “recipes”, which are generally written in the style of a brief abstract of one or more publications on the assay in question. In some cases, but by no means all, the level of detail may almost be sufficient for the interested reader to reproduce the assay in the laboratory. In other cases, the description of the assay protocol amounts to little more than a general overview of the key steps, sometimes interspersed incongruously with one or two very precise experimental details.
These reservations notwithstanding,this book can be a useful resource for scientists in both academia and industry with an interest in drug discovery and medicinal chemistry. The title appears to be targeted mainly at experienced drug discovery practitioners who may use it as a comprehensive reference book. This audience will appreciate that most of the material included in the book reflects the current state-of-the-art in the field, with references running up to and including the year 2008. In keeping with the subtitle, the authors have frequently included references that describe the application of a given assay rather than its development, which allows the reader to gauge the practical usefulness of a particular assay.
Unfortunately, the authors avoid, throughout the book, any discussion of the cellular or biochemical principles behind individual assays, let alone the strengths and limitations of the assays. This is a pity as the authors appear to speak in many cases from their own practical experience. In my opinion, a critical assessment of individual assay protocols, especially where different formats are directly comparable, would have been immensely useful to the interested reader. In the absence of such introductory and explanatory sections, the book is not suitable as a textbook for use, for example, in a postgraduate course on medicinal chemistry and drug discovery (for this purpose, a very good alternative remains the “Handbook of Assay Development in Drug Discovery”, edited by Lisa Minor, Taylor & Francis, 2006). Of course, the authors may not have intended this book to be used as a resource for teaching.
In summary, “Pharmaceutical Bioassays” is a useful reference book for research scientists in drug discovery and medicinal chemistry, providing a comprehensive overview of currently available ioassays. The book has been carefully edited, although figures and other illustrations are used only sparingly. This book is not an introductory text but is ChemMedChem 2010, 5, 958 – 962 2010 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim www.chemmedchem.org 961 aimed at the experienced practitioner—to get the most out of this book, the reader will need to have substantial expertise in the area of drug discovery and the development and application of bioassays.
Dr. Gerd Wagner
University of East Anglia (UK)
DOI: 10.1002/cmdc.201000043
[1] J. C. Milne, P. D. Lambert, S. Schenk, D. P. Carney, J. J. Smith, D. J. Gagne, L. Jin, O. Boss, R. B. Perni, C. B. Vu, J. E. Bemis, R. Xie, J. S. Disch, P. Y. Ng, J. J. Nunes, A. V. Lynch, H. Yang, H. Galonek, K. Israelian, W. Choy, A. Iffland, S. Lavu, O. Medvedik, D. A. Sinclair, J. M. Olefsky, M. R. Jirousek, P. J. Elliott, C. H. Westphal, Nature 2007, 450, 712–716.
[2] D. Beher, J. Wu, S. Cumine, K. W. Kim, S. C. Lu, L. Atangan, M. Wang, Chem. Biol. Drug Des. 2009, 74, 619 –624 .
[3] M. Pacholec, B. A. Chrunyk, D. Cunningham, D. Flynn, D. A. Griffith, M. Griffor, P. Loulakis, B. Pabst, X. Qiu, B. Stockman, V. Thanabal, A. Varghese, J. Ward, J. Withka, K. Ahn, J. Biol. Chem. 2010; DOI:10.1074/jbc.M109.088682.
