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Protein Homeostasis in Drug Discovery
Protein Homeostasis in Drug Discovery Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein’s activity may not be the only factor to consider when developing therapeutic agents. The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discover...
Protein Degradation with New Chemical Modalities
Targeting protein degradation using small molecules is one of the most exciting small-molecule therapeutic strategies in decades and a rapidly growing area of research. In particular, the development of proteolysis targeting chimera (PROTACs) as potential drugs capable of recruiting target proteins to the cellular quality control machinery for elimination has opened new avenues to address traditionally ‘difficult to target’ proteins. This book provides a comprehensive overview from the leading academic and industrial experts on recent developments, scope and limitations in this dynamically growing research area; an ideal reference work for researchers in drug discovery and chemical biology as well as advanced students.
Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and New Targeting Opportunities
MKK7 (MEK7) is a key regulator of the JNK stress signaling pathway and targeting MKK7 has been proposed as a chemotherapeutic strategy. Detailed understanding of the MKK7 structure and factors that impact its activity is therefore of critical importance. Here, we present a comprehensive set of MKK7 crystal structures revealing insights into catalytic domain plasticity and the role of the N-terminal regulatory helix, conserved in all MAP2Ks, mediating kinase activation. Crystal structures harboring this regulatory helix revealed typical structural features of active kinase, providing exclusively a first model of the MAP2K active state. A small molecule screening campaign yielded multiple scaffolds, including type-II irreversible inhibitors a binding mode that has not been reported previously. We also observed an unprecedented allosteric pocket located in the N-terminal lobe for the approved drug ibrutinib. Collectively, our structural and functional data expand and provide alternative targeting strategies for this important MAP2K kinase.
Targeted Protein Degradation
Targeted Protein Degradation, Volume 680 in the Methods in Enzymology series, highlights new advances in the field with this new volume presenting interesting chapters on a variety of timely topics, with each. Each written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in Methods in Enzymology serials Updated release includes the latest information on Targeted Protein Degradation
Making Sense
Breast cancer is one of the most commonly diagnosed cancers and a leading cause of death for women worldwide. With advances in molecular engineering in the 1980s, hopes began to rise that a non-toxic and non-invasive treatment for breast cancer could be developed. These hopes were stoked by the researchers, biotech companies, and analysts who worked to make sense of the uncertainties during product development. In Making Sense Sophie Mützel traces this emergence of "innovative breast cancer therapeutics" from the late 1980s up to 2010, through the lens of the narratives of the involved actors. Combining theories of economic and cultural sociology, Mützel shows how stories are integral for ...
Chemical Biology
An authoritative look at the application of chemical biology in drug discovery and development Based on the award-winning Wiley Encyclopedia of Chemical Biology published in 2008, this book explores the role of chemical biology in drug discovery and development. The first part of the book reviews key principles and techniques used in the design and evaluation of drug candidates. The second part elucidates biological mechanisms of certain diseases, illuminating approaches to investigate and target these diseases. Comprising carefully selected reprints from the Encyclopedia as well as new contributions from leading scholars in the field, this book provides researchers in academia and industry ...
Introduction to Systems Biology
This book is an introduction to the language of systems biology, which is spoken among many disciplines, from biology to engineering. Authors Thomas Sauter and Marco Albrecht draw on a multidisciplinary background and evidence-based learning to facilitate the understanding of biochemical networks, metabolic modeling and system dynamics. Their pedagogic approach briefly highlights core ideas of concepts in a broader interdisciplinary framework to guide a more effective deep dive thereafter. The learning journey starts with the purity of mathematical concepts, reveals its power to connect biological entities in structure and time, and finally introduces physics concepts to tightly align abstra...
Protein Degradation with New Chemical Modalities
Targeting protein degradation using small molecules is one of the most exciting small-molecule therapeutic strategies in decades and a rapidly growing area of research. In particular, the development of proteolysis targeting chimera (PROTACs) as potential drugs capable of recruiting target proteins to the cellular quality control machinery for elimination has opened new avenues to address traditionally 'difficult to target' proteins. This book provides a comprehensive overview from the leading academic and industrial experts on recent developments, scope and limitations in this dynamically growing research area; an ideal reference work for researchers in drug discovery and chemical biology as well as advanced students.
