| 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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