Introduction To Biological And Small Molecule Drug Research And Development

Introduction to Biological and Small Molecule Drug Research and Development provides, for the first time, an introduction to the science behind successful pharmaceutical research and development programs. The book explains basic principles, then compares and contrasts approaches to both biopharmaceuticals (proteins) and small molecule drugs, presenting an overview of the business and management issues of these approaches. The latter part of the book provides carefully selected real-life case studies illustrating how the theory presented in the first part of the book is actually put into practice. Studies include Herceptin/T-DM1, erythropoietin (Epogen/Eprex/NeoRecormon), anti-HIV protease inhibitor Darunavir, and more. Introduction to Biological and Small Molecule Drug Research and Development is intended for late-stage undergraduates or postgraduates studying chemistry (at the biology interface), biochemistry, medicine, pharmacy, medicine, or allied subjects. The book is also useful in a wide variety of science degree courses, in post-graduate taught material (Masters and PhD), and as basic background reading for scientists in the pharmaceutical industry. For the first time, the fundamental scientific principles of biopharmaceuticals and small molecule chemotherapeutics are discussed side-by-side at a basic level Edited by three senior scientists with over 100 years of experience in drug research who have compiled the best scientific comparison of small molecule and biopharmaceuticals approaches to new drugs Illustrated with key examples of important drugs that exemplify the basic principles of pharmaceutical drug research and development

Drug discovery of small molecules from target selection through to clinical evaluation is a very complex, challenging but rewarding area of drug discovery. There are many obstacles along the journey from initial hit-finding activities, through optimization of compounds and eventually to delivery of robust candidate drugs (CDs) for clinical evaluation. This chapter presents key issues and literature solutions with respect to the optimization of hits into CDs. Details of the key hit-finding activities namely high-throughput screening, virtual screening, natural products, fragment-based drug discovery and fast-follower approaches are discussed. Key aspects of compound quality such as lipophilicity, solubility, drug metabolism and pharmacokinetic, plasma protein binding and cytochrome P450 inhibition/induction are discussed as well as potential safety liabilities such as human ether-a-go-go related gene, genotoxicity and phospholipidosis, Finally successful hit-to-lead and lead optimization case studies are presented to illustrate and highlight the key principles.

Successful drugs have a good return on investment by bringing in considerably more revenue than the expenses of discovery, development, and manufacturing. Successful drugs pay for all drug projects, those that fail and those that have yet to fail or succeed. Most research and development (R&D) projects fail. Since R&D is the future of the company, a lot is at stake in the business of R&D. This chapter considers the organization of biopharmaceutical R&D, as well as various organizational experiments, that are already under way, that deal with the enormous risk and cost of biopharmaceutical R&D. There is a fairly uniform sequence of events involved in the discovery and development of biopharmaceuticals. The Stage-Gate Organization of the project pipeline is described along with stage-related goals. The high attrition in the industry is examined as well as reasons for project failure, particularly in the clinic. The fact that most projects fail in the biopharmaceutical industry means that risk, the probability that a project will fail, influences a number of key behaviours in biopharmaceutical R&D. The manner in which risk influences probability of success, cost, value and corporate commitment is considered. Not all discoveries occur within a company – many are in-licenced. Reduced revenues challenge a company's ability to develop all its assets, increasing the demands on project and portfolio management, and for out-licencing or partnering. In large biopharmaceutical companies, resource tends to be organized into business units, therapy areas, line departments, and platform technology groups. In the new era of reduced profits many companies are moving away from vertical integration towards decentralization, performing many to most functions in other companies, and in the extreme, towards virtual drug discovery and development. The risks and benefits with the external allocation of resource via outsourcing and partnering are discussed. Experiments with the organizational model of biopharmaceutical R&D are explored which aim to reduce risk, increase success and efficiency, including attempts to be big and small at the same time, planning for failure, and open innovation. There are also external revenue challenges, including generics competition and third-party payer constraints. On the upside are a number of opportunities to increase revenue, including new biologics and new areas of exploration – epigenetics and gene therapy – and by expanding markets into rapidly developing countries. Managers face complex challenges to the business of biopharmaceutical R&D. But, regardless of the type of company or set of partnered companies, academic institutions and service organizations that perform biopharmaceutical R&D, to a large extent the sequence of events in which a drug is discovered and developed will always be the same. And as long as the industry can continue to find new therapies that positively impact the lives of patients, it will continue to be an exciting and challenging industry.

Small Molecule Drug Discovery: Methods, Molecules and Applications presents the methods used to identify bioactive small molecules, synthetic strategies and techniques to produce novel chemical entities and small molecule libraries, chemoinformatics to characterize and enumerate chemical libraries, and screening methods, including biophysical techniques, virtual screening and phenotypic screening. The second part of the book gives an overview of privileged cyclic small molecules and major classes of natural product-derived small molecules, including carbohydrate-derived compounds, peptides and peptidomimetics, and alkaloid-inspired compounds. The last section comprises an exciting collection of selected case studies on drug discovery enabled by small molecules in the fields of cancer research, CNS diseases and infectious diseases. The discovery of novel molecular entities capable of specific interactions represents a significant challenge in early drug discovery. Small molecules are low molecular weight organic compounds that include natural products and metabolites, as well as drugs and other xenobiotics. When the biological target is well defined and understood, the rational design of small molecule ligands is possible. Alternatively, small molecule libraries are being used for unbiased assays for complex diseases where a target is unknown or multiple factors contribute to a disease pathology. Outlines modern concepts and synthetic strategies underlying the building of small molecules and their chemical libraries useful for drug discovery Provides modern biophysical methods to screening small molecule libraries, including high-throughput screening, small molecule microarrays, phenotypic screening and chemical genetics Presents the most advanced chemoinformatics tools to characterize the structural features of small molecule libraries in terms of chemical diversity and complexity, also including the application of virtual screening approaches Gives an overview of structural features and classification of natural product-derived small molecules, including carbohydrate derivatives, peptides and peptidomimetics, and alkaloid-inspired small molecules

Throughout human history, the morbidity and mortality associated with human disease has driven medical science into an ever-expanding quest for treatment and cure. Over the past century, a therapeutic approach complementing chemical drugs has been developing which uses proteins and peptides in the treatment of disease. Many innovative protein therapeutic platforms are currently being employed and continue to be developed to attain cures in areas of unmet medical need; these include direct copies of natural protein structure and function as well as proteins with completely novel functionality. Today, protein therapeutics represents the fastest growing sector in the pharmaceutical industry and comprises 16% of prescription drug sales in 2011.

Stressing strategic and technological solutions to medicinal chemistry challenges, this book presents methods and practices for optimizing the chemical aspects of drug discovery. Chapters discuss benefits, challenges, case studies, and industry perspectives for improving drug discovery programs with respect to quality and costs. • Focuses on small molecules and their critical role in medicinal chemistry, reviewing chemical and economic advantages, challenges, and trends in the field from industry perspectives • Discusses novel approaches and key topics, like screening collection enhancement, risk sharing, HTS triage, new lead finding approaches, diversity-oriented synthesis, peptidomimetics, natural products, and high throughput medicinal chemistry approaches • Explains how to reduce design-make-test cycle times by integrating medicinal chemistry, physical chemistry, and ADME profiling techniques • Includes descriptive case studies, examples, and applications to illustrate new technologies and provide step-by-step explanations to enable them in a laboratory setting

The third edition of this best-selling book continues to offer a user-friendly, step-by-step introduction to all the key processes involved in bringing a drug to the market, including the performance of pre-clinical studies, the conduct of human clinical trials, regulatory controls, and even the manufacturing processes for pharmaceutical products. Concise and easy to read, Drugs: From Discovery to Approval, Third Edition quickly introduces basic concepts, then moves on to discuss target selection and the drug discovery process for both small and large molecular drugs. The third edition incorporates the latest developments and updates in the pharmaceutical community, provides more comprehensive coverage of topics, and includes more materials and case studies suited to college and university use. Biotechnology is a dynamic field with changes across R&D, clinical trials, manufacturing and regulatory processes, and the third edition of the text provides timely updates for those in this rapidly growing field.

Filled with unique insights into current drugs that have made it to the marketplace In the fifth volume of Successful Drug Discovery, the inventors and primary developers of drugs that made it to the market tell the story of the drugs discovery and development. Case studies of drugs from different therapeutic fields reveal the all-too-often unpredictable path from the first drug candidate molecule to the successfully marketed drug. In addition, this new volume addresses overarching topics for drug discovery, such as drug discovery in academia, and discusses currently important classes of small molecule as well as biological drugs. Comprehensive in scope, the books nine chapters provide a representative cross-section of the present-day drug development effort. The authoritative fifth volume is filled with relevant data and chemical information, as well as the insight and experience of the best contemporary drug creators. This important volume: - Puts the focus on recently introduced drugs that have not yet made it into standard textbooks or general references - Contains information and insight that is new and often not even available from the primary literature - Reveals what it takes to successfully develop a drug molecule that has made it all the way to the market - Is endorsed and supported by the International Union of Pure and Applied Chemistry (IUPAC) Written for medicinal chemists, pharmaceutical chemists, organic chemists, Successful Drug Discovery, Volume Five reveals the most recent techniques used by drug innovators in the drug development process.