A feature story of Lovecraft's celebrated Cthulhu Mythos, "At the Mountains of Madness" is the story of an expedition deep into the barren wastes of Antarctica, where a discovery so horrific and impossible is made that the survivors dare not report the truth until they must to save the lives of another expedition.
An integrated overview of modern approaches to lead discovery Lead generation is increasingly seen as a distinct and success-determining phase of the drug discovery process. Over recent years, there have been major advances in the understanding of what constitutes a good lead compound and how to improve the chances of finding such a compound. Written by leading scientists and established opinion leaders from industry and academia, this book provides an authoritative overview of the field, as well as the theory, practice, and scope, of the principal Lead Generation Approaches in Drug Discovery, including: The evolution of the lead discovery process, key concepts, current challenges, and future directions Strategies and technologies driving the high-throughput screening (HTS) approach to lead discovery, including the shifting paradigms in the design of compound collections and best practice in the hit confirmation process Knowledge-based in silico or «virtual» screening Theory and practice of the fragment-based approach to lead discovery The opportunities and challenges presented by multi-target drug discovery (MTDD) De novo design of lead compounds and new approaches to estimating the synthetic accessibility of de novo–designed molecules The impact of natural products on drug discovery, and potential of natural product–like compounds for exploring regions of biologically relevant chemical space Using early screening of hits and leads for metabolic, pharmacokinetic, and toxicological liabilities to reduce attrition during the later phases of drug discovery The utility of parallel synthesis and purification in lead discovery With each topic supported by numerous case studies, this is indispensable reading for researchers in industry and academia who wish to keep up to date with the latest strategies and approaches in drug discovery.
This book answers the questions about the process and costs of pharmaceutical R & D in a compelling narrative focused on the discovery and development of important new medicines. It gives an insider's account of the pharmaceutical industry drug discovery process, the very real costs of misperceptions about the industry, the high stakes–both economic and scientific–of developing drugs, the triumphs that come when new compounds reach the market and save lives, and the despair that follows when new compounds fail. In the book, John LaMattina, former president of Pfizer Global Research and Development, weaves themes critical to a vital drug discovery environment in the context. This is a story that Dr. LaMattina is uniquely qualified to tell.
A SUNDAY TIMES BOOK OF THE YEAR 'A magnificent, compelling and insightful voyage to the frontier of knowledge from a great writer with a deep understanding.' Brian Cox What is the universe really made of? How do we know? Follow the map of the invisible to find out... Over the last sixty years, scientists around the world have worked together to explore the fundamental constituents of matter, and the forces that govern their behaviour. The result, so far, is the ‘Standard Model’ of elementary particles: a theoretical map of the basic building blocks of the universe. With the discovery of the Higgs boson in 2012, the map as we know it was completed, but also extended into strange new territory. A Map of the Invisible is an explorer’s guide to the Standard Model and the extraordinary realms of particle physics. After shrinking us down to the size of a sub-atomic particle, pioneering physicist Jon Butterworth takes us on board his research vessel for a journey in search of atoms and quarks, electrons and neutrinos, and the forces that shape the universe. Step by step, discovery by discovery, we journey into the world of the unseen, from the atom to black holes and dark matter, and beyond, to the outer reaches of the cosmos and the frontiers of human knowledge. Beautifully illustrated, with gradually evolving maps offering an inventive visual glossary as the journey progresses, A Map of the Invisible provides an essential introduction to our world, and to particle physics. It is a...
The tomb of Tutankhamun, with its treasures, has exerted a hold over the popular imagination ever since its discovery in 1922. This book is a detailed and comprehensive account of this great archaeological discovery. The story of the boy-king, buried in splendour at the height of Egyptian civilization; the determined quest for his tomb by Howard Carter and Lord Carnarvon; the unforeseen riches eventually revealed - these are important events in the history of archaeology. However, despite the publicity at the time of the discovery and since - made more intriguing by the linking of Carnarvon's early death with the legend of the pharoah's curse - it remains a story only partly told. Carter never produced a complete account of his excavations. The Tutankhamun exhibitions of the 1960's and 1970's generated a spate of books but none added significantly to what Carter had already published about the tomb. This book is a revealing account of the subject.Издательство - Thames and Hudson
BACE inhibitors and their use in the treatment of Alzheimer's Disease BACE (β-site of APP cleaving enzyme) is a critical component in Alzheimer's Disease (AD), and the development of BACE inhibitors shows great potential as a therapy for the disease. BACE: Lead Target for Orchestrated Therapy of Alzheimer's Disease covers virtually all aspects of BACE from initial identification, discovery of inhibitors, and challenges in clinical development, while providing a global understanding essential for productive and successful drug discovery. This book details the story of the discovery of BACE and its role in AD and comprehensively discusses: The development of BACE inhibitors as therapeutics for Alzheimer's disease The research that led to the identification of BACE New BACE inhibitors currently being clinically tested ADME (absorption, distribution, metabolism, excretion) and clinical trial design—topics not addressed in current field literature Cutting-edge technology such as high-throughput screening, structure-based drug design, and QSAR in context of BACE inhibitors and Alzheimer's drug discovery Other approaches to BACE inhibition based on interaction with the precursor protein APP By enhancing the reader's understanding of the various aspects of the BACE drug-discovery process, this much-needed reference will serve as a key resource for all scientists involved in Alzheimer's research—and inspire new approaches to treatment of AD.
A comprehensive look at empirical approaches to molecular discovery, their relationships with rational design, and the future of both Empirical methods of discovery, along with serendipitous and rational design approaches, have played an important role in human history. Searching for Molecular Solutions compares empirical discovery strategies for biologically useful molecules with serendipitous discovery and rational design, while also considering the strengths and limitations of empirical pathways to molecular discovery. Logically arranged, this text examines the different modes of molecular discovery, empha-sizing the historical and ongoing importance of empirical strategies. Along with a broad overview of the subject matter, Searching for Molecular Solutions explores: The differing modes of molecular discovery Biological precedents for evolutionary approaches Directed evolutionary methods and related areas Enzyme evolution and design Functional nucleic acid discovery Antibodies and other recognition molecules General aspects of molecular recognition Small molecule discovery approaches Rational molecular design The interplay between empirical and rational strategies and their ongoing roles in the future of molecular discovery Searching for Molecular Solutions covers several major areas of modern research, development, and practical applications of molecular sciences. This text offers empirical-rational principles of broad relevance to scientists, professionals, and students interested in general aspectsof molecular discovery, as well as the thought processes behind experimental approaches. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file.
Retaining the successful approach found in the previous volume in this series, the inventors and primary developers of drugs that successfully made it to market tell the story of the drug's discovery and development and relate the often twisted route from the first candidate molecule to the final marketed drug. 11 selected case studies describe recently introduced drugs that have not been previously covered in textbooks or general references. These range across six different therapeutic fields and provide a representative cross-section of the current drug development efforts. Backed by copious data and chemical information, the insight and experience of the contributors makes this one of the most useful training manuals that a junior medicinal chemist can hope to find and has won the support and endorsement of IUPAC.
The science and applied approaches of enzyme inhibition in drug discovery and development Offering a unique approach that includes both the pharmacologic and pharmaco-kinetic aspects of enzyme inhibition, Enzyme Inhibition in Drug Discovery and Development examines the scientific concepts and experimental approaches related to enzyme inhibition as applied in drug discovery and drug development. With chapters written by over fifty leading experts in their fields, Enzyme Inhibition in Drug Discovery and Development fosters a cross-fertilization of pharmacology, drug metabolism, pharmacokinetics, and toxicology by understanding the «good» inhibitions—desirable pharmacological effects—and «bad» inhibitions—drug–drug interactions and toxicity. The book discusses: The drug discovery process, including drug discovery strategy, medicinal chemistry, analytical chemistry, drug metabolism, pharmacokinetics, and safety biomarker assessment The manipulations of drug metabolizing enzymes and transporters as well as the negative consequences, such as drug–drug interactions The inhibition of several major drug target pathways, such as the GPCR pathway, the NFkB pathway, and the ion channel pathway Through this focused, single-source reference on the fundamentals of drug discovery and development, researchers in drug metabolism and pharmacokinetics (DMPK) will learn and appreciate target biology in drug discovery; discovery biologists and medicinal chemists will also broaden their understanding of DMPK.
Полный вариант заголовка: «The history of the discovery and conquest of the Canary Islands : translated from a Spanish manuscript, lately found in the island of Palma : with an enquiry into the origin of the ancient inhabitants : to which is added, a dsescription of the Canary Islands, including the modern history of the inhabitants, and an account of their manners, customs, trade, & c. / by George Glas».
European thought begins with the Greeks. Scientific and philosophic thinking--the pursuit of truth and the grasping of unchanging principles of life--is a historical development, an achievement; and, as Bruno Snell writes in The Discovery of the Mind, nothing less than a revolution. The Greeks did not take mental resources already at their disposal and merely map out new subjects for discussion and investigation. In poetry, drama, and philosophy they in fact discovered the human mind. The stages in man's gradual understanding of himself are revealed in the course of ancient literature from Homer to Virgil. A rational view of the nature of man slowly established itself in the creations of epic and lyric poetry, tragedy and literary criticism, pre-Socratic thought, and early Greek ethics all the way to the discovery of humanitas and the spiritual landscape of Virgil's Arcadia. The Discovery of the Mind is a landmark work in tracing this evolution of consciousness--one of the distinguishing characteristics of the history of man.
Robert Louis Stevenson (1850-1894) was a Scottish novelist, poet, travel writer, and essayist. He was a celebrity during his lifetime for works like "Strange Case of Dr. Jekyll and Mr. Hyde" and "Treasure Island." Now he is one of the most translated authors in the world. "The Rajah's Diamond" is a collection of four wonderful short stories: "Story of the Bandbox," "Story of the Young Man in Holy Orders," "Story of the House with the Green Blinds," and "The Adventure of Prince Florizel and a Detective."