ChemoinformaticsApproaches to VirtualScreeningEdited by Alexandre Varnek andAlexander Tropsha.

RSC, Cambridge 2008. xvi+338 pp., hardcov-er £ 89.95.—ISBN 978-0-85404-144-2

Virtual screening has become, besideshigh-throughputscreening (HTS), auseful tool for theidentification ofnovel lead struc-tures. The advant-age of the tech-nique is the abilityto search for newlead structureswithin databasesof molecules thatare not physically available.

The term virtual screening is mainly as-sociated with the use of three-dimen-sional structural information on the de-sired target protein to identify potential-ly active compounds. In most cases, thisis the final selection filter of a virtualscreening protocol, and is usually pre-ceded by different ligand-based filtersteps used to reduce the number ofACHTUNGTRENNUNGligands.

This book describes the different tech-niques that can be used for such ligand-based virtual screening filter steps, aswell as pure ligand-based virtual screen-ing protocols. It summarizes all the avail-able state-of-the-art methods in tenchapters written by experts in the field.

Chapter 1 introduces different frag-ment descriptors that can be used forSAR/QSAR/QSPR studies. In Chapters 2and 3, different pharmacophore methodsare presented; Chapter 2 gives an over-view of two-dimensional pharmaco-phores, while in Chapter 3 the differentthree-dimensional pharmacophore ap-proaches are emphasized.

Chapter 4 gives a general introductionto molecular similarity analysis. For new-comers to the field especially, this chap-ter is very valuable, acquainting thereader with the different similarity meas-ures that are applied for ligand-basedvirtual screening methods. Moreover,Chapter 6 also provides an introductionfor newcomers to the field with an over-view of probabilistic approaches in activ-ity prediction, including the applied per-formance measurements.

Molecular field topology analysis is thesubject of Chapter 5. An overview of thistechnique is given for QSAR analysis, aswell as methods for virtual-screening ap-proaches. The design of molecules ishighlighted in Chapters 7 and 9; a frag-ment-based approach for ligand-basedvirtual screening by means of de novodesign is presented in Chapter 7. The ap-proach is described in a step by stepfashion, from fragment generation tode novo molecule generation, and to thefinal scoring of the obtained molecules.In contrast, Chapter 9 provides differentstrategies for compound-library design.

The optimization of drug candidateswith respect to ADME/Tox properties isof utmost importance for successfuldrug development. Therefore, the usageof in silico methods to predict theseproperties in the early stages of a drugresearch project has become increasinglycommon practice. Chapter 8, entitledEarly ADME/T Predictions: Toy or Tool ?, at-tempts to give an answer to this ques-tion. Efforts from different pharmaceuti-cal companies are summarized, and thepitfalls of the applied techniques areidentified and solutions provided.

The final chapter covers the useful as-sembly of chemoinformatic approachesthat, along with traditional structure-based methods (e.g. docking), can beused in virtual-screening protocols forthe successful identification of ligandsfor a desired target. This chapter clearlyshows that both approaches, ligand-

based virtual screening and structure-based virtual screening, greatly enhanceeach other. The concept of using fastchemoinformatic techniques to reducethe number of ligands prior to the appli-cation of computationally expensivemethods with three-dimensional infor-mation is very useful in the light ofgrowing compound databases.

In summary, the book is a compendi-um of reviews that describe differentstate-of the art methods. Every tech-nique presented is discussed in terms ofits applicability to ligand-based virtualscreening. Chemoinformatics Approachesto Virtual Screening, edited by AlexandreVarnek and Alexander Tropsha, serves as

an introductory textbook for students inthe field, as well as a reference book forthe experienced computational chemist.

Dr. Christof Wegscheid-GerlachBayer-Schering Pharma AG (Germany)

Drugs: From Discovery toApproval (2nd ed.)By Rick Ng.

Wiley–Blackwell, Hoboken 2008. xii+466 pp. ,hardcover $ 96.50.—ISBN 978-0-470-19510-9

Drug discovery,development, andregistration havedeveloped into ahighly complex,multistage, inter-disciplinary en-deavor. To com-pile a book cover-ing all essential el-ements from theearly discoveryphases to thefinal stages of registration, discussing all

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key aspects, critical issues, solved andunsolved problems within each stageand discipline would be a formidabletask. For all this to be accomplished byone single author would appear to bealmost impossible. However, that is whatthe author, Dr. Rick Ng, sets out to do.

After a brief introductory overviewover the pharmaceutical R & D process,the book covers, in ten short chapters,the main aspects of target identification,the discovery of small-molecule drugcandidates as well as biopharmaceuti-cals, early development and preclinicalstudies, clinical trials, drug applicationsto regulatory authorities, good manufac-turing practice, and upcoming challeng-es and opportunities at all stages of dis-covery, development, and application.Each chapter is complemented withsummary tables, special exhibits for illus-tration, sometimes one or two case stud-ies, and concludes with review ques-tions, brief answers, explanations, andreferences for further reading.

It comes as no surprise that this bookof ~400 pages cannot provide in-depthdiscussions on all these highly diversetopics. The book thus is primarily direct-ed at nonscientific readers, not involvedin and unfamiliar with the pharmaceuti-cal R & D process, providing a first over-view of the many challenges, critical hur-

dles, pitfalls, many failures, few success-es, partial solutions, and the enormousdevelopment of technologies, methodol-ogies, and new concepts over the lastfew decades, but also the dramatic in-crease in requirements, complexity, andcosts. It may thus help to raise the levelof understanding of laypeople for theenormous difficulties the pharmaceuticaland biotechnology industries are facingwhen attempting to discover and devel-op novel, effective, and selective thera-pies to complex diseases according tohigh modern standards.

Still, the book contains a lot of tech-nological and methodological detail thatwould appear to be unnecessary for anunfamiliar audience and unsuitable forthe informed reader. In many instancesthe representations of technologicalmatters and basic science do not live upto scrutiny and thus do not serve anypurpose. For a subsequent edition, it isthus recommended to critically reviewthese parts of the book and eventuallyreplace them by more insightful discus-sions on the impacts of the variousmethods and technologies.

Likewise, there are a surprisingly highnumber of errors in chemical structures.Of a total of 38 chemical structures re-produced in this book, >60 % (23/38)contain errors. For the nonscientist

reader, this would probably not matter,since chemical structures would beglanced over; and, of course, chemicalstructures of drugs can be easily lookedup in standard repositories. What is ofconcern is the manifestation of a certainlack of attention to the relevant detail.One then wonders whether other mat-ters may be represented with similarlyvarying degree of accuracy. Indeed, anddisturbingly, there are many instances ofinaccurate statements, particularly re-garding methodological and technologi-cal matters. However, most of themwould not affect the main thrust of thebook and the key messages of theauthor.

Hence, and again, the book servesbest for nonscientific readers who wouldlike to get an overview impression of thepharmaceutical R & D process. Since thisprocess continues to undergo dramaticchanges, in concept, technology, andregulation, a third edition will probablybe considered in due course. This thirdedition would evidently benefit a lotfrom a critical scientific and technologi-cal review.

Prof. Klaus M�llerF. Hoffmann–La Roche AG (Switzerland)DOI: 10.1002/cmdc.200900232

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