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.
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.
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».
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.
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.
“An insightful and harrowing roller coaster ride through the career of one of rock and roll’s greatest guitarists. Strap yourself in.” —Slash “Rocking Joe Perry ‘rocks’ again!” —Jimmy Page Before the platinum records or the Super Bowl half-time show or the Rock and Roll Hall of Fame, Joe Perry was a boy growing up in small-town Massachusetts. He idolized Jacques Cousteau and built his own diving rig that he used to explore a local lake. He dreamed of becoming a marine biologist. But Perry’s neighbors had teenage sons, and those sons had electric guitars, and the noise he heard when they started playing would change his life. The guitar became his passion, an object of lust, an outlet for his restlessness and his rebellious soul. That passion quickly blossomed into an obsession, and he got a band together. One night after a performance he met a brash young musician named Steven Tyler; before long, Aerosmith was born. What happened over the next forty-five years has become the stuff of legend: the knockdown, drag-out, band-splintering fights; the drugs, the booze, the rehab; the packed arenas and timeless hits; the reconciliations and the comebacks. Rocks is an unusually searching memoir of a life that spans from the top of the world to the bottom of the barrel—several times. It is a study of endurance and brotherhood, with Perry providing remarkable candor about Tyler, as well as new insights into their powerful but troubled relationship. It is an insider’s portrait of the rock and roll family, featuring everyone from Jimmy Page to Alice Cooper, Bette Midler to Chuck Berry, John Belushi to Al Hirschfeld. It takes us behind the scenes at unbelievable moments such as Joe and Steven’s appearance in the movie of Sgt. Pepper’s Lonely Hearts Club Band (they act out the murders of Peter Frampton and the Bee Gees). Full of humor, insight, and brutal honesty about life in and out of one of the biggest bands in the world, Rocks is the ultimate rock-and-roll epic. In Perry’s own words, it tells the whole story: "the loner’s story, the band’s story, the recovery story, the cult story, the love story, the success story, the failure story, the rebirth story, the re-destruction story, and the post-destructive rebirth story."
The story involves a mine that uncovers a very deep chasm, too deep for any sounding lines to hit bottom. The night after the discovery of the abyss the narrator and one of the mine's workers, Juan Romero, venture inside the mine, drawn against their will by a mysterious rhythmical throbbing in the ground.
Explore the frontier of electronic discovery in the cloud Cloud Computing and Electronic Discovery comprehensively covers the quickly-evolving realm of eDiscovery in cloud computing environments, a computing and legal frontier in which the rules and legal precedents are being developed anew seemingly by the day. The book delves into this fascinating and rapidly-developing topic to prepare fraud investigators, legal professionals, forensic accountants, and executives understand the ramifications of storing data with third party providers and how such storage mechanisms relate to the limits of discovery practices. This up-to-date resource also includes a complete discussion of the few existing legal precedents and current cases that are shaping interpretation of discovery laws in the cloud space, a perfect overview for executives storing their companies' data in the cloud and the legal professionals tasked with understanding and interpreting the discovery rules surrounding that data. The book is comprehensive in scope and includes: An overview of current trends in cloud computing, including potential information that should be considered in an investigation that involves data held by a cloud service provider Updates on current and proposed laws governing discovery of information held by a third party cloud service provider Updates on legal cases that address the issues of the Electronic Communication Privacy Act, the Federal law prohibiting release of information by a third party provider Practical guidance on how to consider the availability of cloud data relevant to an investigation, and how to include this data in discovery plans For business, accounting, and legal professionals, Cloud Computing and Electronic Discovery is an invaluable resource for understanding the nuanced development of cloud eDiscovery policies, practices, and law as they continue to unfold and develop.
The Gene is the story of one of the most powerful and dangerous ideas in our history, from bestselling, prize-winning author Siddhartha Mukherjee. Spanning the globe and several centuries, The Gene is the story of the quest to decipher the master-code that makes and defines humans, that governs our form and function. This is an epic, moving history of a scientific idea coming to life, by the author of The Emperor of All Maladies. But woven through The Gene, like a red line, is also an intimate history – the story of Mukherjee’s own family and its recurring pattern of mental illness, reminding us that genetics is vitally relevant to everyday lives. These concerns reverberate even more urgently today as we learn to “read” and “write” the human genome – unleashing the potential to change the fates and identities of our children. The story of the gene begins in an obscure Augustinian abbey in Moravia in 1856 where a monk stumbles on the idea of a ‘unit of heredity’. It intersects with Darwin’s theory of evolution, and collides with the horrors of Nazi eugenics in the 1940s. The gene transforms post-war biology. It reorganizes our understanding of sexuality, temperament, choice and free will. This is a story driven by human ingenuity and obsessive minds – from Charles Darwin and Gregor Mendel to Francis Crick, James Watson and Rosalind Franklin, and the thousands of scientists still working to understand the code of codes. Majestic in its ambition, and unflinching in its honesty, The Gene gives us a definitive account of the fundamental unit of heredity – and a vision of both humanity’s past and future.
The House by the Churchyard is a novel by Sheridan Le Fanu published in 1863 that combines elements of the mystery novel and the historical novel. Set in the village of Chapelizod, near Dublin, in the 1760s the story opens with the accidental disinterment of an old skull in the churchyard, and an eerie late-night funeral. This discovery relates to murders, both recent and historical whose repercussions disrupt the complacent pace of village affairs and change the lives of many of its notable characters forever. Charm and chilling darkness abound in equal measure in one of the greatest novels of a Victorian master of mystery.
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 Suicide Club" is a collection of three intriguing detective fiction stories set in the nineteenth century: "Story of the Young Man with the Cream Tarts," "Story of the Physician and the Saratoga Trunk," and "The Adventure of the Hansom Cab."