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PARP Inhibitors for Cancer Therapy provides a comprehensive overview of the role of PARP—poly ADP ribose polymerase—in cancer therapy. The volume covers the history of the discovery of PARP and its role in DNA repair. Additionally, it describes the discovery of the PARP family, and includes a discussion of other DNA maintenance-associated PARPs. As well, the volume features a section on the accessible chemistry behind the development of inhibitors. PARP inhibitors—PARPi—are a group of pharmacological inhibitors that are particularly good targets for cancer therapy. PARP plays a pivotal role in DNA repair and may contribute to the therapeutic resistance to DNA-damaging agents used to treat cancer. Researchers have learned a great deal about the biology of PARP and how tumor-specific defects in DNA repair can be exploited by PARPi. The “synthetic lethality” of PARPi is an exciting concept for cancer therapy, and has led to heightened activity in this area.
Biomedicine. --- Cancer Research. --- Drug Resistance. --- Molecular Medicine. --- Medicine. --- Oncology. --- Drug interactions. --- Médecine --- Cancérologie --- Médicaments --- Interaction --- Medicine --- Health & Biological Sciences --- Oncology --- Cancer research. --- Drug resistance. --- Molecular biology. --- Interactions, Drug --- Drugs --- Tumors --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Side effects --- Health Workforce --- NAD-ADP-ribosyltransferase --- Enzyme inhibitors --- Cancer --- Inhibitors --- Therapeutic use. --- Treatment. --- Cancer therapy --- Cancer treatment --- Antagonists, Enzyme --- Enzyme antagonists --- Enzymes --- Inhibitors, Enzyme --- Metabolic inhibitors --- Chemical inhibitors --- ADP-ribosyltransferase (Polymerizing) --- Poly(ADP-ribose) polymerase --- Poly(ADP-ribose) synthase --- Poly(ADP-ribose) synthetase --- Transferases --- Therapy --- Antagonists --- Molecular biochemistry --- Molecular biophysics --- Biochemistry --- Biophysics --- Biomolecules --- Systems biology --- Resistance to drugs --- Pharmacology --- Cancer research
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The kinetic mechanisms by which enzymes interact with inhibitors and activators, collectively called modifiers, are scrutinized and ranked taxonomically into autonomous species in a way similar to that used in the biological classification of plants and animals. The systematization of the mechanisms is based on two fundamental characters: the allosteric linkage between substrate and modifier and the factor by which a modifier affects the catalytic constant of the enzyme. Combinations of the physically significant states of these two characters in an ancestor-descendant-like fashion reveal the existence of seventeen modes of interaction that cover the needs of total, partial and fine-tuning modulation of enzyme activity. These interactions comprise five linear and five hyperbolic inhibition mechanisms, five nonessential activation mechanisms and two hybrid species that manifest either hyperbolic inhibition or nonessential activation characteristics depending on substrate concentration. Five essential activation mechanisms, which are taxonomically independent of the mentioned basic species, complete the inventory of enzyme modifiers. Often masked under conventional umbrella terms or treated as anomalous cases, all seventeen basic inhibition and nonessential activation mechanisms are represented in the biochemical and pharmacological literature of this and the past century, either in the form of rapid or slow-onset reversible interactions, or as irreversible modification processes. The full potential of enzyme inhibitors and activators can only be appreciated after elucidating the details of their kinetic mechanisms of action exploring the entire range of physiologically significant reactant concentrations. This book highlights the wide spectrum of allosteric enzyme modification in physiological occurrences as well as in pharmacological and biotechnological applications that embrace simple and multiple enzyme-modifier interactions. The reader is guided in the journey through this still partly uncharted territory with the aid of mechanistically-oriented criteria aimed at showing the logical way towards the identification of a particular mechanism.
Life Sciences. --- Enzymology. --- Protein-Ligand Interactions. --- Computer Appl. in Life Sciences. --- Biophysics and Biological Physics. --- Life sciences. --- RNA-ligand interactions. --- Enzymes. --- Biology --- Sciences de la vie --- Enzymes --- Biologie --- Data processing. --- Informatique --- Biology_xData processing. --- Chemistry --- Physical Sciences & Mathematics --- Biochemistry --- Enzyme inhibitors. --- Enzyme activation. --- Activation, Enzyme --- Antagonists, Enzyme --- Enzyme antagonists --- Inhibitors, Enzyme --- Metabolic inhibitors --- Antagonists --- Inhibitors --- Proteins. --- Bioinformatics. --- Computational biology. --- Biophysics. --- Biological physics. --- Chemical inhibitors --- Regulation --- Biological and Medical Physics, Biophysics. --- Biocatalysts --- Ferments --- Soluble ferments --- Catalysts --- Proteins --- Enzymology --- Proteins . --- Bioinformatics . --- Computational biology . --- Proteids --- Biomolecules --- Polypeptides --- Proteomics --- Biological physics --- Medical sciences --- Physics --- Bioinformatics --- Bio-informatics --- Biological informatics --- Information science --- Computational biology --- Systems biology --- Data processing
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