{"product_id":"blood-brain-barrier-in-drug-discovery-isbn-9781118788356","title":"Blood-Brain Barrier in Drug Discovery","description":"\u003cp\u003eFocused on central nervous system (CNS) drug discovery efforts, this book educates drug researchers about the blood-brain barrier (BBB) so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery.\u003c\/p\u003e \u003cp\u003e• Written by world experts to provide practical solutions to increase brain penetration or minimize CNS side-effects\u003cbr\u003e • Reviews state-of-the-art in silico, in vitro, and in vivo tools to assess brain penetration and advanced CNS drug delivery strategies\u003cbr\u003e • Covers BBB physiology, medicinal chemistry design principles, free drug hypothesis for the BBB, and transport mechanisms including passive diffusion, uptake\/efflux transporters, and receptor-mediated processes\u003cbr\u003e • Highlights the advances in modelling BBB pharmacokinetics and dynamics relationships (PK\/PD) and physiologically-based pharmacokinetics (PBPK)\u003cbr\u003e • Discusses case studies of successful CNS and non-CNS drugs, lessons learned and paths to the market\u003c\/p\u003e \u003cp\u003eContributors ix\u003c\/p\u003e \u003cp\u003ePreface xiii\u003c\/p\u003e \u003cp\u003e1 Introduction and Overview 1\u003cbr\u003e \u003ci\u003eli di and Edward H. Kerns\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 1 Pharmacokinetics of Brain Exposure 5\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e2 Pharmacokinetics of CNS Penetration 7\u003cbr\u003e \u003ci\u003eAndreas Reichel\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3 Free Drug Hypothesis for CNS Drug Candidates 42\u003cbr\u003e \u003ci\u003eXingrong Liu and Cuiping Chen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4 Species Differences and Impact of Disease State on BBB 66\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJean-Marie Nicolas\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 2 Mechanisms of Drugs Across the Blood–Brain Barrier 95\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e5 Passive Diffusion Permeability of the BBB—Examples and SAR 97\u003cbr\u003e \u003ci\u003eScott Summerfield, Phil Jeffrey, Jasminder Sahi, and Liangfu Chen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6 Establishment of P-Glycoprotein Structure–Transport Relationships to Optimize CNS Exposure in Drug Discovery 113\u003cbr\u003e \u003ci\u003eJerome H. Hochman, Sookhee N. Ha, and Robert P. Sheridan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7 Uptake Transport at the BBB—Examples and SAR 125\u003cbr\u003e \u003ci\u003eZiqiang Cheng and Qian Liu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8 Transport of Protein and Antibody Therapeutics across the Blood–Brain Barrier 146\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eWilliam M. Pardridge\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 3 Predicting and Measuring Brain Exposure of Drugs 167\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e9 In Silico Tools for Predicting Brain Exposure of Drugs 169\u003cbr\u003e \u003ci\u003eHongming Chen, Susanne Winiwarter, and Ola Engkvist\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10 In Vitro Assays for Assessing BBB Permeability: Artificial Membrane and Cell Culture Models 188\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAlex Avdeef, Mária A. Deli, and Winfried Neuhaus\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11 Human-Based In Vitro Brain Endothelial Cell Models 238\u003cbr\u003e \u003ci\u003eHannah K. Wilson and Eric V. Shusta\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12 Methods for Assessing Brain Binding 274\u003cbr\u003e \u003ci\u003eli di and Cheng Chang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13 In Vivo Studies of Brain Exposure in Drug Discovery 284\u003cbr\u003e \u003ci\u003eEdward H. Kerns\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14 PBPK Modeling Approach for Predictions of Human CNS Drug Brain Distribution 296\u003cbr\u003e \u003ci\u003eElizabeth C.M. de Lange\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15 PK\/PD Modeling of CNS Drug Candidates 324\u003cbr\u003e \u003ci\u003eJohan Gabrielsson, Stephan Hjorth, and Lambertus A. Peletier\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16 Microdialysis to Assess Free Drug Concentration in Brain 351\u003cbr\u003e \u003ci\u003eWilliam Kielbasa and Robert E. Stratford, Jr.\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17 Imaging Techniques for Central Nervous System (CNS) Drug Discovery 365\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLei Zhang and Anabella Villalobos\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 4 Modulating Brain Penetration of Leads During Drug Discovery 385\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e18 Designing CNS Drugs for Optimal Brain Exposure 387\u003cbr\u003e \u003ci\u003eZoran Rankovic\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19 Case Studies of CNS Drug Optimization—Medicinal Chemistry and CNS Biology Perspectives 425\u003cbr\u003e \u003ci\u003eKevin J. Hodgetts\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20 Designing Peripheral Drugs for Minimal Brain Exposure 446\u003cbr\u003e \u003ci\u003ePeter Bungay, Sharan Bagal, and Andy Pike\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e21 Case Studies of Non-CNS Drugs to Minimize Brain Penetration—Nonsedative Antihistamines 463\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAndrew Crowe\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 5 Case Studies in CNS Drug Discovery 483\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e22 Case Study 1: The Discovery and Development of Perampanel 485\u003cbr\u003e \u003ci\u003eAntonio Laurenza, Jim Ferry, Haichen Yang, Shigeki Hibi, Takahisa Hanada, and Andrew Satlin\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e23 Case Study 2: The Discovery and Development of the Multimodal Acting Antidepressant Vortioxetine 505\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eChristoffer Bundgaard, Alan L. Pehrson, Connie Sánchez, and Benny Bang-Andersen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 6 Drug Delivery Techniques to CNS 521\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e24 Brain Delivery Using Nanotechnology 523\u003cbr\u003e \u003ci\u003eHuile Gao and Xinguo Jiang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e25 Intranasal Delivery to the Central Nervous System 535\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLisbeth Illum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart 7 Future Prospects in Blood-Brain Barrier Understanding and Drug Discovery 567\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e26 Future Perspectives 569\u003cb\u003e\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eN. Joan Abbott\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIndex 580\u003c\/p\u003e \u003cp\u003e\u003cb\u003eLi Di\u003c\/b\u003e is an associate research fellow in the Pharmacokinetics, Dynamics, and Drug Metabolism Department at Pfizer Global Research and Development and has extensive experience in the pharmaceutical industry. She has over 100 publications, presented over 70 invited lectures, and teaches an American Chemical Society short course on drug-like properties.\u003c\/p\u003e \u003cp\u003e\u003cb\u003eEdward Kerns\u003c\/b\u003e worked in pharmaceutical research and development for over 30 years, was associate director at Wyeth and Bristol-Myers Squibb, then was at the NIH-National Center for Advancing Translational Sciences. He published over 90 journal papers or book chapters and 3 books, and teaches an American Chemical Society short course on drug-like properties.\u003c\/p\u003e  Central nervous system (CNS) drugs are a leading pharmaceutical area, since many CNS diseases remain untreated or without optimum drugs. Unfortunately, the blood-brain barrier (BBB) restricts access of drug molecules circulating in the blood stream to penetrate into the brain cells – and that is where this important book steps in.\u003cbr\u003e \u003cbr\u003e With practical and proven solutions for CNS drug discovery efforts, this book educates drug researchers about the BBB so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery.\u003cbr\u003e \u003cbr\u003e The chapters are written by world-class scientists actively engaged in CNS research from both academia and industry, applying this to more quickly discover and develop better drugs. Among the topics they review are state-of-the-art in silico, in vitro, and in vivo tools for assessing the BBB and advanced delivery technologies. Coverage includes fundamental knowledge about the BBB, implications of these restrictions on free drug exposure at the target in brain, pharmacokinetics (PK) and pharmacodynamics (PD) relationships (PK\/PD), physiologically-based pharmacokinetic (PBPK) brain models, medicinal chemistry design principles, and case studies from successful CNS drug discovery. These case studies examine how the integration of data and design strategies advanced successful new drugs to market.\u003cbr\u003e \u003cbr\u003e A unique and valuable reference resource for practicing medicinal chemists, this book:\u003cbr\u003e \u003cbr\u003e • Focuses on practical solutions of brain exposure problems faced by drug researchers\u003cbr\u003e • Helps readers understand, control and measure the exposure of the drug candidates to the CNS\u003cbr\u003e • Covers BBB physiology; medicinal chemistry design principles; free drug hypothesis for the BBB; and transport mechanisms including passive diffusion, uptake\/efflux transporters and receptor-mediated processes\u003cbr\u003e • Discusses case studies of successful CNS and non-CNS drugs, lessons learned and paths to the market","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47988848623845,"sku":"NP9781118788356","price":166.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9781118788356.jpg?v=1761781763","url":"https:\/\/k12savings.com\/es\/products\/blood-brain-barrier-in-drug-discovery-isbn-9781118788356","provider":"K12savings","version":"1.0","type":"link"}