| 1. |
- Andersson, Claes R., et al.
(författare)
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Quantitative Chemogenomics : Machine-Learning Models of Protein-Ligand Interaction
- 2011
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 11:15, s. 1978-1993
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Forskningsöversikt (refereegranskat)abstract
- Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed.
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| 2. |
- Burnstock, G, et al.
(författare)
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Adenosine and ATP receptors in the brain
- 2011
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Ingår i: Current topics in medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1873-4294 .- 1568-0266. ; 11:8, s. 973-1011
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Danielson, U Helena
(författare)
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Fragment library screening and lead characterization using SPR biosensors
- 2009
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 9:18, s. 1725-1735
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Tidskriftsartikel (refereegranskat)abstract
- The transition from high throughput screening of collections of drug-like compounds to screening of fragment libraries via lower throughput methods with high sensitivity has revolutionized early drug discovery. It is highlighting the need for sensitive biophysical techniques for interaction analysis rather than high throughput methods. Biosensors with SPR detection are well suited for this novel scenario. In less than 20 years the technique has been launched, established and become a highly informative method for a variety of applications in drug discovery. It is no longer limited to the detection of proteins or other high molecular weight analytes, but the detection of weakly interacting fragments is now feasible. This paper discusses the theoretical and experimental limitations for such applications and reviews a number of successful studies in the area of fragment-based lead discovery that have recently been published. It can be anticipated that the evolution of this young technique will be significantly influenced by the requirements for efficient fragment-based lead discovery.
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| 4. |
- Das, Alakesh, et al.
(författare)
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A concise review on the role of natural and synthetically derived peptides involved in colorectal cancer
- 2022
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers. - 1568-0266 .- 1873-4294. ; 22:31, s. 2571-2588
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Forskningsöversikt (refereegranskat)abstract
- Colorectal cancer being the second leading cause of cancer-associated deaths, it has become a significant health concern around the globe. Though there are various counts of cancer treatment approaches, many of them show adverse effects and further compromise the condition of the cancer patients. Hence, significant exertions are conducted for the evolution of a novel biological therapeutic approach with better efficacy and minimal side effects. Current research suggests that the application of peptides in colorectal cancer therapeutics holds the possibility of a emerging anticancer reagent. The primary beneficial factors of peptides are their comparatively rapid and easy process of synthesis and the enormous potential for chemical alterations that can be evaluated for designing novel peptides and enhancing the delivery capacity of peptides. Peptides might be utilized as agents with cytotoxic activities or as a carrier of a specific drug or cytotoxic agents that can efficiently target the tumor cells. Further, peptides can also be used as a tool for diagnostic purposes. The recent analysis aims at developing peptides that have the potential to efficiently target the tumor moieties without harming the nearby normal cells. Additionally, decreasing the adverse effects, and unfolding the other therapeutic properties of potential peptides, are also the subject matter of in-depth analysis. This review provides a concise summary of the function of both natural and synthetically derived peptides in colorectal cancer therapeutics that are recently being evaluated and their potent applications in the clinical field.
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| 5. |
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| 6. |
- Fowler, Christopher J, et al.
(författare)
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Targeting the endocannabinoid system for the treatment of cancer : a practical view
- 2010
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers. - 1568-0266 .- 1873-4294. ; 10:8, s. 814-827
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Forskningsöversikt (refereegranskat)abstract
- In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells. In the present review, the potential of targeting the cannabinoid system for the treatment of cancer is considered from a practical, rather than a mechanistic viewpoint, addressing questions such as whether human tumour cells express CB receptors; whether the potencies of action of cannabinoids in vitro match the potencies expected on the base of receptor theory; what is known about the in vivo effects of cannabinoids and cancer, and how relevant the experiments undertaken are to the clinical situation; and finally, what approaches can be taken to minimise unwanted effects of cannabinoid treatment. It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area, but that more in vivo studies, particularly those investigating the potential of cannabinoids as an addition to current treatment strategies, are needed.
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| 7. |
- Gutiérrez-de-Terán, Hugo, et al.
(författare)
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Structure-Based Rational Design of Adenosine Receptor Ligands
- 2017
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 17:1, s. 40-58
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Forskningsöversikt (refereegranskat)abstract
- The family of adenosine receptors (ARs) is focus of several medicinal chemistry programs aimed to find new potent and selective drugs. Each receptor subtype has been proposed as a relevant drug target in the treatment of, e.g., cardiovascular or inflammatory diseases, asthma or Parkinson's disease. Until recently, most of these efforts have been dominated by ligand-based or empirical approaches. However, the latest advances in G protein-coupled receptor (GPCR) crystallography allowed for a thorough structural characterization of the A(2A)AR subtype, which has been crystalized with a number of agonists and antagonists. Consequently, the ligand discovery of AR ligands has been enriched with a number of structure-based approaches. These include the generation of higher-confident homology models for the remaining AR subtypes, virtual screening identification of novel chemotypes, structure-based lead-optimization programs, rationalization of selectivity profiles, or the structural characterization of novel binding sites that enable the design of novel allosteric modulators. Computational methodologies have importantly contributed to the success of these structure-based approaches, and the recent advances in the field are also analyzed in this review. We conclude that the design of adenosine receptor ligands has improved dramatically with the consideration of structure-based approaches, which is paving the way to a better understanding of the biology and pharmacological modulation of this relevant family of receptors.
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| 8. |
- Hammarlund-Udenaes, Margareta, et al.
(författare)
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Methodologies to assess brain drug delivery in lead optimization
- 2009
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 9:2, s. 148-162
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Forskningsöversikt (refereegranskat)abstract
- In the area of lead optimization for potential CNS-active drugs in medicinal chemistry, there is a great need for experimental methodologies that can generate data relevant to estimates of free (unbound) drug exposure within the CNS. The methods chosen have to be efficient and have to measure a pharmacologically relevant entity. The lack of methods for generating such data is probably linked with the lack of successful lead optimization strategies within CNS drug discovery. This article evaluates available methods for estimating drug delivery to the brain, and discusses the relevance of the methods from the perspective of CNS exposure to free drug. It is suggested that the extent of drug delivery is the most important investigative parameter, since permeability (rate of transfer) can vary within a relatively wide range and still allow effects within the CNS. Following this suggestion would shift the focus from the current way of thinking and could lead to the development of less lipophilic compounds than are currently being investigated. It is concluded that an extensive collection of quality data on brain drug delivery, transporter affinities and in vivo behavior is urgently required so as to be able to build relevant predictive in vitro and in silico models for the future. These models need to be much more focused on the asymmetry of active transport across the BBB than on permeability data.
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| 9. |
- Hernandez, Luiza I, et al.
(författare)
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Aptamers overview : selection, features and applications.
- 2015
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham science publishers. - 1568-0266 .- 1873-4294. ; 15:12, s. 1066-1081
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Tidskriftsartikel (refereegranskat)abstract
- Apatamer technology has been around for a quarter of a century and the field had matured enough to start seeing real applications, especially in the medical field. Since their discovery, aptamers rapidly emerged as key players in many fields, such as diagnostics, drug discovery, food science, drug delivery and therapeutics. Because of their synthetic nature, aptamers are evolving at an exponential rate gaining from the newest advances in chemistry, nanotechnology, biology and medicine. This review is meant to give an overview of the aptamer field, by including general aspects of aptamer identification and applications as well as highlighting certain features that contribute to their quick deployment in the biomedical field.
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| 10. |
- Hu, Fanjie, et al.
(författare)
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Imidazole Scaffold Based Compounds in the Development of Therapeutic Drugs
- 2021
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Ingår i: Current Topics in Medicinal Chemistry. - Oak Park, IL : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 21:28, s. 2514-2528
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Tidskriftsartikel (refereegranskat)abstract
- Imidazole has an important five-membered aromatic heterocyclic ring, which is available widely in natural products and synthetic molecules. The special structural characteristics of imidazole ring enable it to bind with a variety of enzymes and receptors through hydrogen bonds, coordination, ion-dipole and cation-π interactions, hydrophobic effects, and Van der Waals forces. These interactions promote several biological activities involving anti-tumor, anti-inflammatory, anti-microbial, and anti-viral properties. Herein, we review and discuss recent developments in using imidazole derivatives and their special pharmacological activities for the treatment of various diseases. © 2021 Bentham Science Publishers.
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| 11. |
- Jothimani, Ganesan, et al.
(författare)
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A Review on Theragnostic Applications of microRNAs and Long Non-Coding RNAs in Colorectal Cancer
- 2018
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Ingår i: Current Topics in Medicinal Chemistry. - : BENTHAM SCIENCE PUBL LTD. - 1568-0266 .- 1873-4294. ; 18:30, s. 2614-2629
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Forskningsöversikt (refereegranskat)abstract
- Colorectal cancer (CRC) is a heterogeneous malignancy leading to increased mortality and poor prognosis due to the lack of efficient early diagnostics. Metastasis of the tumor being the most common cause of mortality is accountable for almost 90% of CRC associated deaths. Intensified screening procedures and molecular target identification has inflated the median survival rate of in CRC patients. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have come forward as potential targets for developing a novel approach in CRC theragnostics. Non-coding RNA (ncRNAs) sequences are abundantly present and thereby play a vital role in several biological processes such as cellular organization, cell fate determination, proliferation, apoptosis, tissue homeostasis maintenance as well as pathological conditions such as cancer by acting as post transcriptional regulators of gene expression. Several studies have highlighted the involvement of these ncRNAs in CRC development. However, the molecular mechanism involved in regulating CRC has not been clearly elucidated. This review, throws light upon the several non-coding RNAs involved in CRC with a focus on novel mechanisms of action, recent advances in the regulatory mechanisms that control the gene expression related to carcinogenesis. Furthermore, the potential role of ncRNAs as diagnostic as well as therapeutic targets has been reviewed.
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| 12. |
- Kaur, Upinder, et al.
(författare)
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Reactive Oxygen Species, Redox Signaling and Neuroinflammation in Alzheimers Disease: The NF-kappa B Connection
- 2015
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Ingår i: Current Topics in Medicinal Chemistry. - : BENTHAM SCIENCE PUBL LTD. - 1568-0266 .- 1873-4294. ; 15:5, s. 446-457
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Forskningsöversikt (refereegranskat)abstract
- Oxidative stress and inflammatory response are important elements of Alzheimers disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-kappa B and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD. The possibility of identifying new disease-modifying drugs for AD targeting NF-kappa B signaling cascade has been discussed in the end.
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| 13. |
- Malmsten, Martin
(författare)
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Interactions of Antimicrobial Peptides with Bacterial Membranes and Membrane Components
- 2015
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 16:1, s. 16-24
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Forskningsöversikt (refereegranskat)abstract
- Antimicrobial peptides (AMPs) have attracted considerable recent interest as potential therapeutics, motivated by increasing resistance development against conventional antibiotics. This brief overview summarizes some key aspects related to the interaction of AMPs with bacterial and cell membranes, as well as with membrane components, which is at the core of the mode-of-action of these compounds. Throughout, studies on peptide interactions with model lipid membranes and membrane components are correlated to biological results on antimicrobial and anti-inflammatory effects of AMPs, and translated into therapeutic considerations.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Prachayasittikul, Veda, et al.
(författare)
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Computer-Aided Drug Design of Bioactive Natural Products.
- 2015
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 15:18, s. 1780-800
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Tidskriftsartikel (refereegranskat)abstract
- Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world's health population and well-being.
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| 18. |
- Rodríguez, David, et al.
(författare)
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Discovery of GPCR Ligands by Molecular Docking Screening : Novel Opportunities Provided by Crystal Structures
- 2015
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 15:24, s. 2484-2503
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Forskningsöversikt (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) constitute the largest group of human membrane proteins and have received significant attention in drug discovery for their important roles in physiological processes. Drug development for GPCRs has been remarkably successful and several of the most profitable pharmaceuticals on the market target members of this superfamily. Breakthroughs in structural biology for GPCRs have revealed how their binding sites recognize extracellular molecules at the atomic level. High-resolution crystal structures of GPCR-drug complexes capturing different receptor conformations are now available, which have provided insights into how ligands stabilize different functional states. Recently, the basis for subtype selectivity and novel allosteric binding sites has also been revealed by crystal structures. These accomplishments provide exciting opportunities to identify novel GPCR ligands using in silico structure-based methods such as molecular docking. Increased computational power now enables docking screens of large chemical libraries to identify molecules that complement GPCR binding sites, which may provide possibilities to identify ligands with tailored pharmacological properties. This review focuses on prospective docking screens against GPCRs and how this technique can be used to identify lead candidates with specific signaling or selectivity profiles. The current state of this field suggests that molecular docking, in combination with further understanding of GPCR signaling, will play an important role in future drug discovery.
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| 19. |
- Rönn, Robert, et al.
(författare)
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New developments in the discovery of agents to treat hepatitis C
- 2008
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 8:7, s. 533-562
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Forskningsöversikt (refereegranskat)abstract
- Hepatitis C virus (HCV) has deceived researchers for seventeen years now and although the current therapy regimen has been optimized by the development of pegylated interferon-alpha and the addition of ribavirin, no new agent to treat HCV infected patients has yet reached the market. A new era is approaching the HCV research due to new developments for the propagation of the virus in a cell-based system, which may lead to new drug innovations. Efforts in the search of new treatments for HCV infected patients are either focused on direct antiviral drugs, targeting the structural components or enzymes encoded by the virus, or indirect antiviral drugs, targeting host cell components (immunomodulators etc.). An inspection of the drug pipeline for HCV reveals representatives from both classes and of different mechanisms of action. Among the direct acting antiviral agents, inhibitors of the NS3 protease, the NS5B polymerase, and the viral RNA are the most intensively explored. However, there is also on-going and promising preclinical research, in different stages, on other potential targets as the structural protein E2 (for cell-entry inhibitors), the NS3 helicase, the p7 ion-channel, and the multifunctional NS5A protein. The combat of HCV will certainly require a combination of drugs of different mechanisms in order to reduce the emergence of resistance. The latest developments in the discovery of agents to treat HCV are reviewed, with special focus on direct small-molecule antiviral drugs, from a medicinal chemistry perspective.
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| 20. |
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| 21. |
- Sgaramella, Nicola, et al.
(författare)
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Searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck, with specific focus on tumours of the tongue
- 2018
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers. - 1568-0266 .- 1873-4294. ; 18:3, s. 214-218
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Forskningsöversikt (refereegranskat)abstract
- Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning the site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide, an increasing number of people ≤ 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group. Even without any clinical signs of metastasis, up to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In this mini review, field cancerization, tumour microenvironment, the so called EMT (epithelial mesenchymal transition) process and the role of viruses in development of SCCHN are discussed as well as potential new therapeutic targets. For the group of tongue SCC, with the increasing incidence seen in young patients and particularly women, new data with impact on prognosis and treatment are urgently needed. But as long as data from the analyses of several sub sites are presented as valid for the whole group of tumours, this vital point is missed.
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| 22. |
- Spjuth, Ola, 1977-, et al.
(författare)
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Open source drug discovery with Bioclipse
- 2012
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 12:18, s. 1980-1986
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Forskningsöversikt (refereegranskat)abstract
- We present the open source components for drug discovery that has been developed and integrated into the graphical workbench Bioclipse. Building on a solid open source cheminformatics core, Bioclipse has advanced functionality for managing and visualizing chemical structures and related information. The features presented here include QSAR/QSPR modeling, various predictive solutions such as decision support for chemical liability assessment, site-of-metabolism prediction, virtual screening, and knowledge discovery and integration. We demonstrate the utility of the described tools with examples from computational pharmacology, toxicology, and ADME. Bioclipse is used in both academia and industry, and is a good example of open source leading to new solutions for drug discovery.
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| 23. |
- Syvänen, Stina, et al.
(författare)
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Using PET Studies of P-gp Function to Elucidate Mechanisms Underlying the Disposition of Drugs
- 2010
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 10:17, s. 1799-1809
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Forskningsöversikt (refereegranskat)abstract
- This paper discusses the basic principles of drug/P-glycoprotein (P-gp) interaction, focusing on the methodology and design of positron emission tomography (PET) studies investigating P-gp function. The requirements of a good PET P-gp radiotracer are also evaluated. (R)-[C-11]verapamil is used as an example, as this drug is the most common tracer for P-gp studies, but [C-11]loperamide, [C-11]desmethyl-loperamide and other compounds are also mentioned. The article also discusses the various study designs that can be used for PET drug disposition studies, such as administration of the inhibitor before or after the radiolabeled drug (tracer) and the use of bolus injections or infusions. Concepts such as the unbound partition coefficient (K-p,K-uu) and the volume of distribution of unbound drug in brain (V-u,V-brain), which are not easily measured directly with PET, can be used to describe the impact of protein binding and non-specific binding on drug distribution in brain tissue. It is concluded that new imaging probes will be required if the role of PET in studies of the interactions of drugs with efflux transporters is to expand.
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| 24. |
- Thompson, Philip E., et al.
(författare)
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Re-discovering PDE3 inhibitors - New opportunities for a long neglected target
- 2007
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1873-4294 .- 1568-0266. ; 7:4, s. 421-436
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Forskningsöversikt (refereegranskat)abstract
- The PDE3 enzymes or "low Kin cGMP-inhibited phosphodiesterases" have long been established as important mediators of cellular physiology, and synthetic PDE3 inhibitors have been critical to the delineation of the enzymes' roles. Yet despite decades of progress on the biology of these enzymes, the medicinal chemistry landscape relating to PDE3 inhibitors has remained essentially unchanged since the mid 1990's. Up until then the field was at the cutting edge of drug design; without the tools of molecular and structural biology, molecules of high potency were being achieved using logical pharmacophore models and lead modification. Yet virtually all the impetus went out of this area on the back of failures at the clinic and PDE3 as a therapeutic target largely fell out of favour. A decade later and with the "new" technologies of structural and molecular biology breathing new life into PDE3 research in general, PDE3 inhibitors are sought for target validation in an array of therapeutic applications. In this review, we examine the current state of PDE3 research; firstly we summarize the structural and functional properties of PDE3 enzymes with particular attention to the heterogeneity within this class of enzymes which differ markedly in expression, localisation and means of regulation across various tissue types. It is the structural and functional complexity of the PDE3 enzymes that underpins the re-emergence of PDE3s roles as targets for drug design. We then took at past clinical evaluation of PDE3 inhibitors that occurred without that. information and which may have had a significant bearing on the outcome of those drug discovery efforts. Finally we look at current approaches to the design of PDE3 inhibitors which utilize that historic data but also incorporate new inputs from structural biology and combinatorial chemistry.
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| 25. |
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| 26. |
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| 27. |
- Martin-Rodriguez, AJ
(författare)
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Recent Advances in Anti-biofilm Strategies
- 2017
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Ingår i: CURRENT TOPICS IN MEDICINAL CHEMISTRY. - : Bentham Science Publishers Ltd.. - 1568-0266. ; 17:17, s. 1887-1888
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Sun, Delin, et al.
(författare)
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Current understanding of the mechanisms by which membrane-active peptides permeate and disrupt model lipid membranes
- 2016
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266. ; 16:2, s. 170-186
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Forskningsöversikt (refereegranskat)abstract
- Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes. On the other hand, AMPs also show evidence of rapid translocation, but associated with this, is membrane rupture to form large pores, which are subsequently stabilized by peptide adsorption to the pore edges. This disruption to the membrane is presumably responsible for cell death. Amyloidal peptides also show evidence of stable large pore formation, however, the mechanism for pore stabilization appears linked with their ability to form fibrils and prefibrillar aggregates and oligomers. There is some evidence that pores and membrane defects in fact act as nucleation sites for these structures. Where possible we have related the experimental and theoretical work to our own simulation findings in an effort to produce a comprehensive, albeit speculative picture for the mechanisms of action for this important group of peptides.
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| 29. |
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| 30. |
- Zhang, HY, et al.
(författare)
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RNA Interference with chemically modified siRNA
- 2006
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Ingår i: Current topics in medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266. ; 6:9, s. 893-900
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Tidskriftsartikel (refereegranskat)
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| 31. |
- Kröger, Ronald
(författare)
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Optical plasticity in fish lenses.
- 2013
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Ingår i: Progress in Retinal and Eye Research. - : Elsevier BV. - 1873-1635 .- 1350-9462. ; 34:Online 20 December 2012, s. 78-88
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Tidskriftsartikel (refereegranskat)abstract
- In a typical fish eye, the crystalline lens is the only refractive element. It is spherical in shape and has high refractive power. Most fish species have elaborate color vision and spectral sensitivity may range from the near-infrared to the near-ultraviolet. Longitudinal chromatic aberration exceeds depth of focus and chromatic blur is compensated for by species-specific multifocality of the lens. The complex optical properties of fish lenses are subject to accurate regulation, including circadian reversible adjustments and irreversible developmental tuning. The mechanisms optimize the transfer of visual information to the retina in diverse and variable environments, and allow for rapid evolutionary changes in color vision. Active optical tuning of the lens is achieved by changes in the refractive index gradient and involves layers of mature, denucleated lens fiber cells. First steps have been taken toward unraveling the signaling systems controlling lens optical plasticity. Multifocal lenses compensating for chromatic blur are common in all major groups of vertebrates, including birds and mammals. Furthermore, the optical quality of a monofocal lens, such as in the human eye, is equally sensitive to the exact shape of the refractive index profile. Optical plasticity in the crystalline lens may thus be present in vertebrates in general.
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