Download or read book Modeling Inhibitors of Matrix Metalloproteinases written by Tarun Jha and published by CRC Press. This book was released on 2023-12-29 with total page 491 pages. Available in PDF, EPUB and Kindle. Book excerpt: Matrix metalloproteinases (MMPs) have been established as promising biomolecular targets for novel drug design and discovery against numerous major disease conditions including various cancers, cardiovascular, neurodegenerative, inflammatory diseases, and more. This book covers various modern molecular modeling methodologies particularly related to MMP inhibitors. Included in the text are descriptions of ligand-based drug designing and structure-based drug designing modeling strategies for designing potential and target specific or selective MMPIs. This book will benefit those who are looking for an in-depth text on the design and discovery processes of novel and selective MMPIs. Features Describes modeling strategies applied to MMPs Elaborates on the designing strategies of MMPs specifically Includes in-depth analyses of related case studies Acts as a guide for medicinal chemists, not only from pharmaceutical industries, but also from academia Covers various modern molecular modeling methodologies, particularly related to MMPIs

Download or read book Matrix Metalloproteinase Inhibitors in Cancer Therapy written by Neil J. Clendeninn and published by Springer Science & Business Media. This book was released on 2000-09-17 with total page 371 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

Download or read book Molecular Modeling of Matrix Metalloproteinases and Their Inhibitors written by Gitte Elgaard Terp and published by . This book was released on 2001 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Metal Containing Enzymes written by and published by Academic Press. This book was released on 2014-11-24 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Published continuously since 1944, the Advances in Protein Chemistry and Structural Biology series is the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics. - Describes advances in metal-containing enzymes - Chapters are written by authorities in their field - Targeted to a wide audience of researchers, specialists, and students - The information provided in the volume is well supported by a number of high quality illustrations, figures, and tables

Download or read book Tetracyclines in Biology Chemistry and Medicine written by M. Nelson and published by Springer Science & Business Media. This book was released on 2001-10-01 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: The tetracyclines have an illustrious history as therapeutic agents which dates back over half a century. Initially discovered as an antibiotic in 1947, the four ringed molecule has captured the fancy of chemists and biologists over the ensuing decades. Of further interest, as described in the chapter by George Armelagos, tetracyclines were already part of earlier cultures, 1500-1700 years ago, as revealed in traces of drug found in Sudanese Nubian mummies. The diversity of chapters which this book presents to the reader should illus trate the many disciplines which have examined and seen benefits from these fascinating natural molecules. From antibacterial to anti-inflammatory to anti autoimmunity to gene regulation, tetracyclines have been modified and redesigned for various novel properties. Some have called this molecule a biol ogist's dream because of its versatility, but others have seen it as a chemist's nightmare because of the synthetic chemistry challenges and "chameleon-like" properties (see the chapter by S. Schneider).

Download or read book Matrix Metalloproteinase Inhibitors written by Satya Prakash Gupta and published by Springer Science & Business Media. This book was released on 2012-04-05 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

Download or read book A Bioinorganic Approach to Matrix Metalloproteinase Inhibition written by David Thomas Puerta and published by . This book was released on 2006 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt: In an effort to develop potent inhibitors of matrix metalloproteinases (MMPs), a bioinorganic approach was employed. The synthesis of [(TpPh, Me)Zn(OH)] provided for a structural analogue of the zinc-(tris-histidine) catalytic site of MMPs. The model complex was used to gain insight into the discrepancy of MMP inhibitor (MPI) potencies between mercapto alcohols and mercapto ketones. This initial experiment validated the use of the inorganic model complex as a structural model of the MMP catalytic site. Novel ZBGs for incorporation into MPIs were identified. These ZBGs were complexed with [(TpPh, Me)Zn(OH)] to obtain structural information such as binding mode, bond lengths, and coordination geometry. All ZBG examined were found to bind the model complex in a bidentate fashion, indicating promise for incorporation into a full length MPI. The inhibitory ability of the novel ZBGs was examined in both fluorescent and colorimetric assays using either the catalytic domain of MMPs or native enzyme expressed in a cell culture of neonatal rat ventricular fibroblasts. All novel ZBGs examined were found to be better inhibitors of MMPs in vitro and in cell culture assays than acetohydroxamic acid (the representative ZBG used in the majority of MPIs to date). In order to design full-length MPIs, a combined computational-bioinorganic method was developed. Using the structural coordinates from the [(TpPh, Me)Zn(ZBG)] complexes, the novel ZBGs were modeled into an X-ray crystal structure of uninhibited MMP-3. This study allowed for the examination of the ZBGs in the active site of an MMP. The novel ZBGs were found to have orientations in the active site of MMP-3 amendable to the attachment of a peptidomimetic backbone, necessary for a full-length MPI. Finally, the first MPIs based on the heterocyclic ZBGs were developed. The combined computational-bioinorganic method was augmented with the drug discovery program LUDI. Using LUDI enhanced with structural coordinates from [(TpPh, Me)Zn(3-hydroxy-2-methyl-4-pyrone)], several MPIs were designed. The potential inhibitors were synthesized and were examined in a fluorescence-based assay of MMP-1, -2, and -3. The pyrone-based MPIs were found to be more potent than their hydroxamate analogues, demonstrating the efficacy of a bioinorganic approach to the development of metalloprotein inhibitors.

Download or read book Matrix Metalloproteinase Inhibitors written by Satya Prakash Gupta and published by Springer. This book was released on 2012-04-11 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

Download or read book Snake Venom Metalloproteinases written by Jay Fox and published by MDPI. This book was released on 2018-07-10 with total page 277 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Snake Venom Metalloproteinases" that was published in Toxins

Download or read book Medicinal Chemistry of Anticancer Drugs written by Carmen Avendaño and published by Elsevier. This book was released on 2015-06-11 with total page 767 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicinal Chemistry of Anticancer Drugs, Second Edition, provides an updated treatment from the point of view of medicinal chemistry and drug design, focusing on the mechanism of action of antitumor drugs from the molecular level, and on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents. Antitumor chemotherapy is a very active field of research, and a huge amount of information on the topic is generated every year. Cytotoxic chemotherapy is gradually being supplemented by a new generation of drugs that recognize specific targets on the surface or inside cancer cells, and resistance to antitumor drugs continues to be investigated. While these therapies are in their infancy, they hold promise of more effective therapies with fewer side effects. Although many books are available that deal with clinical aspects of cancer chemotherapy, this book provides a sorely needed update from the point of view of medicinal chemistry and drug design. - Presents information in a clear and concise way using a large number of figures - Historical background provides insights on how the process of drug discovery in the anticancer field has evolved - Extensive references to primary literature

Download or read book Drug like Properties Concepts Structure Design and Methods written by Li Di and published by Elsevier. This book was released on 2010-07-26 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint

Download or read book Inhibition of Matrix Metalloproteinases written by Robert A. Greenwald and published by . This book was released on 1999 with total page 792 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume contains papers from a multidisciplinary conference convened to discuss mechanisms of action, pharmacology, models for drug development, and recent positive clinical trial data relating to the inhibition of collagenases and related metalloproteinases matrix (MMPs). Excess metalloproteinase activity has been identified in many disease processes, and finally products for the specific use as metalloproteinase inhibitors are about to be marketed. In this book, two novel themes are explored: the arguments for and against broad-spectrum versus specific MMP inhibitors, and the potential usefulness of chairside diagnostic kits for clinical determination of excessive MMP activity.

Download or read book Matrix Metalloproteinase Biology written by Irit Sagi and published by John Wiley & Sons. This book was released on 2015-05-27 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discussing recent advances in the field of matrix metalloproteinase (MMP) research from a multidisciplinary perspective, Matrix Metalloproteinase Biologyis a collection of chapters written by leaders in the field of MMPs. The book focuses on the challenges of understanding the mechanisms substrate degradation by MMPs, as well as how these enzymes are able to degrade large, highly ordered substrates such as collagen. All topics addressed are considered in relation to disease progression including roles in cancer metastasis, rheumatoid arthritis and other inflammatory diseases. The text first provides an overview of MMPs, focusing on the history, the development and failures of small molecule inhibitors in clinical trials, and work with TIMPS, the endogenous inhibitors of MMPs. These introductory chapters establish the foundation for later discussion of the recent progress on the design of different types of inhibitors, including novel antibody based therapeutics. The following section emphasizes research using novel methods to further the study of the MMPs. The third and final section focuses on in vivo research, particularly with respect to cancer models, degradation of the extracellular matrix, and MMP involvement in other disease states. Written and edited by leaders in the field, Matrix Metalloproteinase Biology addresses the rapidly growth in MMP research, and will be an invaluable resource to advanced students and researchers studying cell and molecular biology.

Download or read book Matrix Metalloproteinases in Health and Disease written by Raffaele Serra and published by . This book was released on 2020-09-11 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt: Matrix metalloproteinases (MMPs) are members of an enzyme family and are critical for maintaining tissue allostasis. MMPs can catalyze normal turnover of the extracellular matrix (ECM) together with other metalloproteinases such as ADAM (a disintegrin and metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) families. MMP activity is also regulated by a group of endogenous proteins called tissue inhibitor of metalloproteinases (TIMPs). All these proteins have a pivotal role involving ECM remodelling in normal physiological processes such as wound healing, embryogenesis, angiogenesis, bone remodelling, immunity, and the female reproductive cycle. An imbalance in the expression or activity of MMPs can also have important consequences in diseases such as cancer, cardiovascular disease, peripheral vascular disease, chronic leg ulcers, and multiple sclerosis. In recent years, MMPs have been found to play an important role in the field of precision medicine, as they may serve as biomarkers that may predict an individual's disease predisposition, state, or progression. MMPs are also thought to be a sensible target for molecular therapy. The aim of this Special Issue is to explore the most recent findings in this field that may have an impact in healthcare systems.

Download or read book Zinc Metalloproteases In Health And Disease written by NM Hooper and published by CRC Press. This book was released on 1996-07-30 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: The zinc metalloproteases are a diverse group of enzymes which are becoming increasingly important in a variety of biological systems. Their major function is to break down proteins. This text presents recent research results on the biochemistry and molecular biology of these enzymes.

Download or read book Matrix Metalloproteinases and Tissue Remodeling in Health and Disease Target Tissues and Therapy written by and published by Academic Press. This book was released on 2017-06-26 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy, Volume, Volume 148, the latest volume in the Progress in Molecular Biology and Translational Science series covers a variety of timely topics, with chapters focusing on The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs, Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target, Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy, Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia, and Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology. This volume is the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease. It focuses on the role of MMPs in other systems, target tissues, and pathological disorders and the potential benefits of MMP inhibitors in various disorders.

Download or read book In Search of MMP Specific Inhibitors written by Harinathachari Bahudhanapati and published by . This book was released on 2009 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs). Since unregulated MMP activities are linked to arthritis, cancer, and atherosclerosis, TIMP variants that are selective inhibitors of disease-related MMPs have potential therapeutic value. The structures of TIMP/MMP complexes reveal that most interactions with the MMP involve the N-terminal region of TIMP and the CD-ß-strand connector which occupy the primed (right side of the active site) and unprimed (left side) regions of the active site. Substitutions for Thr2 of N-TIMP- 1 strongly influence MMP selectivity. In this study we found that Arg and Gly, which generally reduce MMP affinity, have less effect on binding to MMP-9. When the Arg mutation is added to the NTIMP-1 mutant with AB loop of TIMP-2, it produced a gelatinase-specific inhibitor with Ki values of 2.8 and 0.4 nM for MMP-2 and MMP-9, respectively. The Gly mutant has a Ki of 2.1 nM for MMP-9 and > 40 uM for MMP-2, indicating that engineered TIMPs can discriminate between MMPs in the same subfamily. In collaboration with Dr. Yingnan Zhang at Genentech, we have developed a protocol for the phage display of full-length human TIMP-2 to identify high-affinity selective inhibitors of human MMP-1, a protease that plays a role in cleaving extracellular matrix (ECM) components, connective tissue remodeling during development, angiogenesis, and apoptosis. We have generated a library containing 2x1010 variants of TIMP-2 randomized at residues 2-6 (L1), at residues 34-40 (L2) and 67-70 (L3). The L1 library yielded a positive signal for MMP-1 binding. Clones from the L1 library, designated TM1, TM8, TM13, and TM14, were isolated after 5 rounds of selection on immobilized MMP-1 and MMP-3 and found to show a greater selectivity for MMP-1 relative to MMP-3. TM8, which has Ser2 to Asp and Ser4 to Ala substitutions, showed the greatest apparent selectivity of 10-fold toward MMP-1 compared to MMP-3. The various mutations identified by phage display were introduced into recombinant Nterminal TIMP-2 and the variants characterized as inhibitors of an array of MMP catalytic domains. The TM8-based mutant showed pronounced selectivity (> 1000-fold for MMP-1 vs. MMP-3) and may be a step towards the generation of MMP-1-specific inhibitors. Molecular modeling was used to rationalize the structural basis of MMP-selectivity in the mutants.