1,327 results match your criteria Expert Opinion on Drug Discovery[Journal]


Why have transgenic rodent models failed to successfully mimic Alzheimer's disease. How can we develop effective drugs without them?

Expert Opin Drug Discov 2019 Feb 18:1-4. Epub 2019 Feb 18.

b CiberNed: Centro de Investigación en Red, enfermedades Neurodegenerativas , Instituto de Salud Carlos III , Madrid , Spain.

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http://dx.doi.org/10.1080/17460441.2019.1581169DOI Listing
February 2019

Recent developments in biological aspects of chalcones: the odyssey continues.

Expert Opin Drug Discov 2019 Mar;14(3):249-288

a Department of Chemistry , Guru Nanak Dev University , Amritsar , India.

Introduction: Chalcones are attractive to synthetic chemists because they are easy to prepare, have a large number of replaceable hydrogens, thereby having significant biological potential. Chalcones and their derivatives (carbocyclic as well as heterocyclic) exhibit a range of biological properties including anticancer, antimalarial, antioxidant, anti-inflammatory and anti-tubercular activities. Their promising biological profile, along with their ease of synthetic manipulations, have triggered the design and development of new chalcone derivatives as well as their conjugates with active pharmacophores affording therapeutic templates targeting various diseases. Read More

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http://dx.doi.org/10.1080/17460441.2019.1573812DOI Listing

Carbohydrate-protein interactions and multivalency: implications for the inhibition of influenza A virus infections.

Expert Opin Drug Discov 2019 Feb 5:1-9. Epub 2019 Feb 5.

a Department of Chemical Biology & Drug Discovery , Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht , The Netherlands.

Introduction: Protein-carbohydrate interactions play a very important role in many biological processes. A single interaction between a protein and a carbohydrate is usually weak, but multivalent ligands can compensate for this deficiency by binding multiple binding sites to one biological entity simultaneously. Over the past few years, numerous efforts have been made for the design and synthesis of carbohydrate-based multivalent ligands thereby serving as potent inhibitors for pathogens such as the influenza A virus. Read More

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http://dx.doi.org/10.1080/17460441.2019.1573813DOI Listing
February 2019

Successes, failures, and future prospects of prodrugs and their clinical impact.

Expert Opin Drug Discov 2019 Mar 4;14(3):199-220. Epub 2019 Feb 4.

a Department of Bioorganic & Pharmaceutical Chemistry, Faculty of Pharmacy , Al-Quds University , Jerusalem , Palestine.

Introduction: Ample efforts have been carried out to improve the efficacy of a variety of drugs. The prodrugs approach was found to be a safe haven for providing medications with improved pharmacokinetic and pharmacodynamic properties. Areas covered: Herein, several selected successful prodrugs are reported and categorized. Read More

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http://dx.doi.org/10.1080/17460441.2019.1567487DOI Listing
March 2019
3.467 Impact Factor

Animal models of ischemic stroke and their impact on drug discovery.

Expert Opin Drug Discov 2019 Mar 4;14(3):315-326. Epub 2019 Feb 4.

c Department of Neurology , University Medicine Göttingen , Göttingen , Germany.

Introduction: Representing the leading cause of long-term disability, ischemic stroke urgently needs further research and drug development. This review summarizes current animal models of ischemic stroke that can be used for drug discovery. Areas covered: Several reproducible models of permanent and transient focal cerebral ischemia have been established in a variety of animal species including rats and mice, in which a brain-supplying artery, often the middle cerebral artery, is occluded by mechanical devices including sutures, clips and hooks, pharmacological agents or delivery of blot clots. Read More

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https://www.tandfonline.com/doi/full/10.1080/17460441.2019.1
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http://dx.doi.org/10.1080/17460441.2019.1573984DOI Listing
March 2019
3 Reads

Could advances in representation learning in Artificial Intelligence provide the new paradigm for data integration in drug discovery?

Expert Opin Drug Discov 2019 Mar 30;14(3):191-194. Epub 2019 Jan 30.

a Computational Biology , GlaxoSmithKline R&D , Collegeville , PA , USA.

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http://dx.doi.org/10.1080/17460441.2019.1573811DOI Listing
March 2019
4 Reads

Anticancer drug discovery using multicellular tumor spheroid models.

Expert Opin Drug Discov 2019 Mar 28;14(3):289-301. Epub 2019 Jan 28.

a Biosciences Laboratory , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.

Introduction: Despite the increasing financial outlay on cancer research and drug discovery, many advanced cancers remain incurable. One possible strategy for increasing the approval rate of new anticancer drugs for use in clinical practice could be represented by three-dimensional (3D) tumor models on which to perform in vitro drug screening. There is a general consensus among the scientific community that 3D tumor models more closely recapitulate the complexity of tumor tissue architecture and biology than bi-dimensional cell cultures. Read More

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http://dx.doi.org/10.1080/17460441.2019.1570129DOI Listing
March 2019
1 Read

Novel approaches for designing drugs that interfere with pH regulation.

Expert Opin Drug Discov 2019 Mar 25;14(3):231-248. Epub 2019 Jan 25.

a NEUROFARBA Department, Sezione di Scienze Farmaceutiche , University of Florence , Sesto Fiorentino (Florence) , Italy.

Introduction: In all living species, pH regulation is a tightly controlled process, with a plethora of proteins involved in its regulation. These include sodium-proton exchangers, carbonic anhydrases, anion exchangers, bicarbonate transporters/cotransporters, H-ATPases, and monocarboxylate transporters. All of them play crucial roles in acid-base balancing, both in eukaryotic as well as in prokaryotic organisms, making them interesting drug targets for the management of pathological events (in)directly involved in pH regulation. Read More

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https://www.tandfonline.com/doi/full/10.1080/17460441.2019.1
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http://dx.doi.org/10.1080/17460441.2019.1567488DOI Listing
March 2019
3 Reads

Inkjet dispensing technologies: recent advances for novel drug discovery.

Expert Opin Drug Discov 2019 Feb 24;14(2):101-113. Epub 2019 Jan 24.

b Joint Department of Biomedical Engineering , University of North Carolina and North Carolina State University , Raleigh , NC , USA.

Introduction: Inkjet-dispensing printing is a promising additive manufacturing method for pharmaceutical applications such as drug discovery. The unique advantages of this technology, including low cost, programmability, high resolution, high throughput, high speed, and biocompatibility, may reduce the financial resources needed to discover new drug candidates. Sophisticated and miniaturized assays have been developed to accomplish drug discovery and drug screening using modern inkjet dispensing printers. Read More

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http://dx.doi.org/10.1080/17460441.2019.1567489DOI Listing
February 2019
1 Read

Strategies to optimize drug half-life in lead candidate identification.

Expert Opin Drug Discov 2019 Mar 24;14(3):221-230. Epub 2019 Jan 24.

a Department of Drug Metabolism and Pharmacokinetics , Genentech , South San Francisco , CA , USA.

Introduction: The PK optimization of drug candidates is one of the most resource-intensive tasks in pharmaceutical research and development. With the increasing availability of in silico, in vitro and mechanistic in vivo ADME models, drug discovery scientists have progressively learned to recognize common SAR patterns and engineer data-driven strategies to accelerate the resolution of ADME issues in lead optimization. Many of these strategies gravitate toward the concept of drug-likeness, which defines a number of optimal holistic physicochemical parameters (such as lipophilicity) that idealized oral drugs possess. Read More

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http://dx.doi.org/10.1080/17460441.2019.1569625DOI Listing

An assessment of the translational relevance of Drosophila in drug discovery.

Expert Opin Drug Discov 2019 Mar 21;14(3):303-313. Epub 2019 Jan 21.

a Division of Neuroscience , Biomedical Sciences Research Centre "Alexander Fleming" , Vari , Greece.

Introduction: Drosophila melanogaster offers a powerful expedient and economical system with facile genetics. Because of the high sequence and functional conservation with human disease-associated genes, it has been cardinal in deciphering disease mechanisms at the genetic and molecular level. Drosophila are amenable to and respond well to pharmaceutical treatment which coupled to their genetic tractability has led to discovery, repositioning, and validation of a number of compounds. Read More

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http://dx.doi.org/10.1080/17460441.2019.1569624DOI Listing
March 2019
1 Read

Animal models for modeling pancreatic cancer and novel drug discovery.

Expert Opin Drug Discov 2019 Feb 18;14(2):127-142. Epub 2019 Jan 18.

a Department of Internal Medicine 3 , University Hospital of Bonn , Bonn , Germany.

Introduction: Despite the introduction of novel therapeutic regimens for advanced stages of pancreatic cancer, long-term survival and overall outcome for patients are still very poor. Suitable small animal models are a prerequisite for better understanding of underlying pathophysiology and for translational studies designed to uncover novel therapeutic targets and to evaluate therapy regimens on a preclinical level. Areas covered: Genetically engineered mouse models as well as syngenic and xenotransplantation models are summarized and critically discussed with respect to their value for pancreatic cancer translational research. Read More

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https://www.tandfonline.com/doi/full/10.1080/17460441.2019.1
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http://dx.doi.org/10.1080/17460441.2019.1566319DOI Listing
February 2019
2 Reads

The impact of perampanel and targeting AMPA transmission on anti-seizure drug discovery.

Expert Opin Drug Discov 2019 Mar 11;14(3):195-197. Epub 2019 Jan 11.

b Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health , University of Genoa, "G. Gaslini" Institute , Genova , Italy.

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http://dx.doi.org/10.1080/17460441.2019.1566318DOI Listing

The identification of small molecules that stimulate retinal pigment epithelial cells: potential novel therapeutic options for treating retinopathies.

Expert Opin Drug Discov 2019 Feb 8;14(2):169-177. Epub 2019 Jan 8.

a Stem Cell Therapies in Neurodegenerative Diseases Lab , Research Center "Principe Felipe" , Valencia , Spain.

Introduction: Combinatory strategies using pharmacology and stem cell therapy have emerged due to their potential in the treatment of retinal pigment epithelium (RPE) cell related diseases, and a variety of different stem cell sources have been evaluated both in animal models and in humans. RPE cells derived from human embryonic stem cells (hESCs) and human induced pluripotent cells (hiPSCs) are already in clinical trials, holding great promise for the treatment of age-related macular disease (AMD) and hereditary RPE-related retinal dystrophies. Highly efficient protocol for RPE generations have been developed, but they are still time-consuming and laborious. Read More

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http://dx.doi.org/10.1080/17460441.2019.1559148DOI Listing
February 2019

Novel antiviral drug discovery strategies to tackle drug-resistant mutants of influenza virus strains.

Expert Opin Drug Discov 2019 Feb 26;14(2):153-168. Epub 2018 Dec 26.

b Department of Biotechnology , College of Life Science and Biotechnology, Yonsei University , Seoul , South Korea.

Introduction: The emergence of drug-resistant influenza virus strains highlights the need for new antiviral therapeutics to combat future pandemic outbreaks as well as continuing seasonal cycles of influenza. Areas covered: This review summarizes the mechanisms of current FDA-approved anti-influenza drugs and patterns of resistance to those drugs. It also discusses potential novel targets for broad-spectrum antiviral drugs and recent progress in novel drug design to overcome drug resistance in influenza. Read More

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http://dx.doi.org/10.1080/17460441.2019.1560261DOI Listing
February 2019
2 Reads

Enabling drug discovery and development through single-cell imaging.

Expert Opin Drug Discov 2019 Feb 24;14(2):115-125. Epub 2018 Dec 24.

d Alliance Management and Partnering , Novartis Institutes for BioMedical Research Inc ., Emeryville , CA , USA.

Introduction: Single-cell imaging-based assays are an area of active and growing investment in drug discovery and development. This approach offers researchers the capability to interrogate rare subpopulations of cells with minimal sample consumption and multiplexed readouts. Recent technological advances in the optical interrogation and manipulation of single cells have substantially increased the throughput and sensitivity of these assays. Read More

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http://dx.doi.org/10.1080/17460441.2019.1559147DOI Listing
February 2019
1 Read

Drug design strategies for Cushing's syndrome.

Expert Opin Drug Discov 2019 Feb 20;14(2):143-151. Epub 2018 Dec 20.

a Institute of Bioorganic Chemistry of the National Academy of Science of Belarus , Minsk , Republic of Belarus.

Introduction: Cushing's syndrome (CS) is a metabolic disorder caused by chronic hypercortisolism. CS is associated with cardiovascular, metabolic, skeletal and psychological dysfunctions and can be fatal if left untreated. The first-line treatment for all forms of CS is a surgery. Read More

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http://dx.doi.org/10.1080/17460441.2019.1559146DOI Listing
February 2019
3 Reads

Lamotrigine as a mood stabilizer: insights from the pre-clinical evidence.

Expert Opin Drug Discov 2019 Feb 7;14(2):179-190. Epub 2018 Dec 7.

a Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina , Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.

Introduction: Lamotrigine (LTG) is a well-established anticonvulsant that is also approved for the prevention of mood relapses in bipolar disorder. However, the mechanisms underlying LTG mood stabilizing effects remain unclear. Areas covered: Herein, the pre-clinical evidence concerning LTG's' mode of action in depression and mania is reviewed. Read More

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http://dx.doi.org/10.1080/17460441.2019.1553951DOI Listing
February 2019
3 Reads

Organ-on-a-chip technologies that can transform ophthalmic drug discovery and disease modeling.

Expert Opin Drug Discov 2019 Jan 8;14(1):47-57. Epub 2018 Dec 8.

b Department of Women's Health, Research Institute for Women's Health , Eberhard Karls University Tübingen , Tübingen , Germany.

Introduction: Disorders of the eye that lead to visual impairment are affecting millions of people worldwide. Nevertheless, for many of these disorders, there are still no effective treatment options available due to the lack of in vitro model systems that emulate the physiological in vivo structure and function of human eyes. Microphysiological organ-on-a-chip (OoC) technology represents a novel and powerful approach to overcome the limitations of conventional model systems and lead to a paradigm shift in ophthalmic research. Read More

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http://dx.doi.org/10.1080/17460441.2019.1551873DOI Listing
January 2019
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Optimization techniques for novel c-Met kinase inhibitors.

Expert Opin Drug Discov 2019 Jan 5;14(1):59-69. Epub 2018 Dec 5.

b State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences , Nanjing University , Nanjing , China.

Introduction: c-Met kinase plays an important part in the regulation of cell growth, invasion and anti-apoptosis. This enzyme is also an important target in cancer treatment. Through structural optimization and structure-activity studies of drugs currently on the market and those still in clinical trials, a great number of novel c-Met kinase inhibitors have been developed. Read More

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http://dx.doi.org/10.1080/17460441.2019.1551355DOI Listing
January 2019

Challenges with risk mitigation in academic drug discovery: finding the best solution.

Authors:
Anuradha Roy

Expert Opin Drug Discov 2019 Feb 4;14(2):95-100. Epub 2018 Dec 4.

a High Throughput Screening laboratory , University of Kansas , Lawrence , KS , USA.

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http://dx.doi.org/10.1080/17460441.2019.1553952DOI Listing
February 2019
8 Reads

Advances with support vector machines for novel drug discovery.

Expert Opin Drug Discov 2019 Jan 29;14(1):23-33. Epub 2018 Nov 29.

c Escola de Artes, Ciências e Humanidades , Universidade de São Paulo (USP) , São Paulo , Brazil.

Introduction: Novel drug discovery remains an enormous challenge, with various computer-aided drug design (CADD) approaches having been widely employed for this purpose. CADD, specifically the commonly used support vector machines (SVMs), can employ machine learning techniques. SVMs and their variations offer numerous drug discovery applications, which range from the classification of substances (as active or inactive) to the construction of regression models and the ranking/virtual screening of databased compounds. Read More

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http://dx.doi.org/10.1080/17460441.2019.1549033DOI Listing
January 2019
11 Reads

Closed-loop discovery platform integration is needed for artificial intelligence to make an impact in drug discovery.

Expert Opin Drug Discov 2019 Jan 29;14(1):1-4. Epub 2018 Nov 29.

b Kebotix Inc ., Cambridge , MA , USA.

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http://dx.doi.org/10.1080/17460441.2019.1546690DOI Listing
January 2019
1 Read
3.467 Impact Factor

Drug-based cancer therapy to overcome immune resistance by steering tumor evolution.

Authors:
Ariel Fernández

Expert Opin Drug Discov 2019 Jan 29;14(1):5-8. Epub 2018 Nov 29.

a Ariel Fernandez Innovation, Pharmaceutical Consultancy , Buenos Aires.

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http://dx.doi.org/10.1080/17460441.2019.1550066DOI Listing
January 2019

Advances in distributed computing with modern drug discovery.

Expert Opin Drug Discov 2019 Jan 13;14(1):9-22. Epub 2018 Dec 13.

a Bioinformatics and High Performance Computing Research Group (BIO-HPC) , Universidad Católica de Murcia (UCAM) , Murcia , Spain.

Introduction: Computational chemistry dramatically accelerates the drug discovery process and high-performance computing (HPC) can be used to speed up the most expensive calculations. Supporting a local HPC infrastructure is both costly and time-consuming, and, therefore, many research groups are moving from in-house solutions to remote-distributed computing platforms. Areas covered: The authors focus on the use of distributed technologies, solutions, and infrastructures to gain access to HPC capabilities, software tools, and datasets to run the complex simulations required in computational drug discovery (CDD). Read More

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http://dx.doi.org/10.1080/17460441.2019.1552936DOI Listing
January 2019
1 Read
3.467 Impact Factor

Current developments in lantibiotic discovery for treating Clostridium difficile infection.

Expert Opin Drug Discov 2019 Jan 27;14(1):71-79. Epub 2018 Nov 27.

a Alderley Park Macclesfield , Evotec , Cheshire , UK.

Introduction: Clostridium difficile is a major cause of healthcare-associated diarrhea linked to the misuse of antimicrobials and the corresponding deleterious impact they have on the protective microbiota of the gut. Resistance to agents used to treat C. difficile including metronizadole and vancomycin has been reported highlighting the need for novel agents. Read More

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http://dx.doi.org/10.1080/17460441.2019.1549032DOI Listing
January 2019
19 Reads

Advances and challenges in drug design against tuberculosis: application of in silico approaches.

Expert Opin Drug Discov 2019 Jan 26;14(1):35-46. Epub 2018 Nov 26.

a Laboratoire d'Optique et Biosciences (CNRS UMR7645, INSERM U1182) , Ecole Polytechnique , Palaiseau , France.

Introduction: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains the deadliest infectious disease in the world with one-third of the world's population thought to be infected. Over the years, TB mortality rate has been largely reduced; however, this progress has been threatened by the increasing appearance of multidrug-resistant Mtb. Considerable recent efforts have been undertaken to develop new generation antituberculosis drugs. Read More

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http://dx.doi.org/10.1080/17460441.2019.1550482DOI Listing
January 2019
12 Reads

Steps to address anti-microbial drug resistance in today's drug discovery.

Authors:
Tanya Parish

Expert Opin Drug Discov 2019 Feb 22;14(2):91-94. Epub 2018 Nov 22.

a TB Discovery Research , Infectious Disease Research Institute , Seattle , WA , USA.

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http://dx.doi.org/10.1080/17460441.2019.1550481DOI Listing
February 2019
1 Read

Using virtual reality for drug discovery: a promising new outlet for novel leads.

Expert Opin Drug Discov 2018 Nov 20:1-12. Epub 2018 Nov 20.

b Key Laboratory of Biomass Chemical Engineering of Ministry of Education , College of Chemical and Biological Engineering, Zhejiang University , Hangzhou , China.

Introduction: Virtual reality (VR) environments are increasingly being used by researchers in various fields in addition to being increasingly integrated into various areas of human life, ranging from videogames to different industrial uses. VR can be used to create interactive and multimodal sensory stimuli and thus offers unique advantages over other computer-based approaches for scientific research and molecular-level applications. Consequently, VR is starting to be used in novel drug development, such as in drug discovery, and rational drug design. Read More

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http://dx.doi.org/10.1080/17460441.2018.1546286DOI Listing
November 2018
1 Read

Vortioxetine: a novel antidepressant for the treatment of major depressive disorder.

Expert Opin Drug Discov 2019 Jan 20;14(1):81-89. Epub 2018 Nov 20.

e Department of Psychiatry and Neuroscience Program, Harvard Medical School , McLean Hospital , Belmont , USA.

Introduction: Vortioxetine is a novel antidepressant drug approved for the treatment of major depressive disorder (MDD) in adults. It is formulated into tablets and has a dose range of 5-20 mg. The recommended starting dose is 10 mg administered orally once daily without the need for food. Read More

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http://dx.doi.org/10.1080/17460441.2019.1546691DOI Listing
January 2019
10 Reads
3.467 Impact Factor

An overview of neural networks for drug discovery and the inputs used.

Expert Opin Drug Discov 2018 Nov 17:1-12. Epub 2018 Nov 17.

a Department of Medicinal Chemistry, School of Pharmacy , China Pharmaceutical University , Nanjing , China.

Introduction: Artificial intelligence systems based on neural networks (NNs) find rules for drug discovery according to training molecules, but first, the molecules need to be represented in certain ways. Molecular descriptors and fingerprints have been used as inputs for artificial neural networks (ANNs) for a long time, while other ways for describing molecules are used only for storing and presenting molecules. With the development of deep learning, variants of ANNs are now able to use different kinds of inputs, which provide researchers with more choices for drug discovery. Read More

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http://dx.doi.org/10.1080/17460441.2018.1547278DOI Listing
November 2018

Chromones: privileged scaffolds for the production of multi-target-directed-ligand agents for the treatment of Alzheimer's disease.

Expert Opin Drug Discov 2018 Nov 15:1-11. Epub 2018 Nov 15.

a Department of Chemistry & QOPNA , University of Aveiro , Aveiro , Portugal.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder responsible for the great majority of age-related dementias affecting daily life through memory loss and cognitive impairment. From a molecular point of view, the most common neuropathological characteristics found in AD patients are abnormal protein deposits, particularly senile plaques (SP) and neurofibrillary tangles (NFT). Furthermore, the currently available pharmacological treatment only provides short-term improvements and is focused on the use of cholinesterase (ChEs) inhibitors or memantine, an approved medicine that is a glutamatergic N-methyl-D-aspartate (NMDA) receptor blocker. Read More

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http://dx.doi.org/10.1080/17460441.2018.1543267DOI Listing
November 2018
19 Reads

Developments with 3D bioprinting for novel drug discovery.

Expert Opin Drug Discov 2018 Nov 1:1-15. Epub 2018 Nov 1.

b Engineering Science and Mechanics Department , Penn State University , University Park , PA , USA.

Introduction: Although there have been significant contributions from the pharmaceutical industry to clinical practice, several diseases remain unconquered, with the discovery of new drugs remaining a paramount objective. The actual process of drug discovery involves many steps including pre-clinical and clinical testing, which are highly time- and resource-consuming, driving researchers to improve the process efficiency. The shift of modelling technology from two-dimensions (2D) to three-dimensions (3D) is one of such advancements. Read More

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http://dx.doi.org/10.1080/17460441.2018.1542427DOI Listing
November 2018

Current approaches for choosing feature selection and learning algorithms in quantitative structure-activity relationships (QSAR).

Expert Opin Drug Discov 2018 Dec 3;13(12):1075-1089. Epub 2018 Nov 3.

b Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology , Jadavpur University , Kolkata , India.

Introduction: Quantitative structure-activity/property relationships (QSAR/QSPR) are statistical models which quantitatively correlate quantitative chemical structure information (described as molecular descriptors) to the response end points (biological activity, property, toxicity, etc.). Important strategies for QSAR model development and validation include dataset curation, variable selection, and dataset division, selection of modeling algorithms and appropriate measures of model validation. Read More

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http://dx.doi.org/10.1080/17460441.2018.1542428DOI Listing
December 2018
8 Reads

Gaussian accelerated molecular dynamics for elucidation of drug pathways.

Expert Opin Drug Discov 2018 Nov 29;13(11):1055-1065. Epub 2018 Oct 29.

a Center for Computational Biology and Department of Molecular Biosciences , University of Kansas , Lawrence, KS , USA.

Introduction: Understanding pathways and mechanisms of drug binding to receptors is important for rational drug design. Remarkable advances in supercomputing and methodological developments have opened a new era for application of computer simulations in predicting drug-receptor interactions at an atomistic level. Gaussian accelerated molecular dynamics (GaMD) is a computational enhanced sampling technique that works by adding a harmonic boost potential to reduce energy barriers. Read More

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http://dx.doi.org/10.1080/17460441.2018.1538207DOI Listing
November 2018
6 Reads

Animal models used to assess influenza antivirals.

Expert Opin Drug Discov 2018 Dec 30;13(12):1131-1139. Epub 2018 Oct 30.

a WHO Collaborating Centre for Reference and Research on Influenza , VIDRL, Peter Doherty Institute for Infection and Immunity , Melbourne , Australia.

Introduction: Influenza continues to be a major public health concern. Antivirals play an important role in limiting the burden of disease and preventing infection and/or transmission. The developments of such agents are heavily dependent on pre-clinical evaluation where animal models are used to answer questions that cannot be easily addressed in human clinical trials. Read More

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http://dx.doi.org/10.1080/17460441.2018.1540586DOI Listing
December 2018
12 Reads

Challenges and ethical considerations for using cloned primates for human brain discovery.

Expert Opin Drug Discov 2018 Dec 25;13(12):1071-1074. Epub 2018 Oct 25.

a Hudson Institute of Medical Research , Monash University , Clayton , Australia.

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http://dx.doi.org/10.1080/17460441.2018.1540585DOI Listing
December 2018
9 Reads

Preclinical discovery and development of colesevelam for the treatment of type 2 diabetes.

Expert Opin Drug Discov 2018 Oct 19:1-7. Epub 2018 Oct 19.

a Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.

Introduction: Type 2 diabetes (T2D) is a major global health challenge associated with increased cardiovascular morbidity and mortality. Intervention strategies managing multiple risk factors (hyperglycemia, hypertension and dyslipidemia) in patients with T2D can reduce the risk of cardiovascular disease by ~50%. Areas covered: Herein, the authors provide an update on the development and clinical potential of colesevelam as a glucose-lowering drug in T2D. Read More

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https://www.tandfonline.com/doi/full/10.1080/17460441.2018.1
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http://dx.doi.org/10.1080/17460441.2018.1538206DOI Listing
October 2018
4 Reads

Targeting adenosine A receptor antagonism for treatment of cancer.

Expert Opin Drug Discov 2018 Nov 18;13(11):997-1003. Epub 2018 Oct 18.

c Medicinal Chemistry, Oncology , IMED Biotech Unit, AstraZeneca , Boston , MA , USA.

Introduction: Adenosine A Receptor (AR) antagonists are an emerging class of agents that treat cancers, both as a monotherapy and in combination with other therapeutic agents. Several studies support the accumulation of extracellular adenosine in the tumor microenvironment as a critical mechanism in immune evasion implicating AR antagonists for use in immuno-oncology. Areas covered: In this perspective article, the authors briefly outline the history of the AR antagonist field for central nervous system indications and give their perspective on the status of agents progressing today in oncology. Read More

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http://dx.doi.org/10.1080/17460441.2018.1534825DOI Listing
November 2018
9 Reads

How far have decision tree models come for data mining in drug discovery?

Expert Opin Drug Discov 2018 Dec 23;13(12):1067-1069. Epub 2018 Oct 23.

a Division of Clinical Pharmacology and Toxicology, Department of Clinical Research and Department of Internal Medicine , University Hospital Basel, University of Basel , Basel , Switzerland.

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http://dx.doi.org/10.1080/17460441.2018.1538208DOI Listing
December 2018
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Development of transplant immunosuppressive agents - considerations in the use of animal models.

Expert Opin Drug Discov 2018 Nov 17;13(11):1041-1053. Epub 2018 Oct 17.

c Department of Transplant Surgery , City Hospital , Belfast , UK.

Introduction: The development of all immunosuppressant agents to date has involved the experimental use of large and small animal models. Over the last half-century, immunosuppressive drugs have extended the lives of transplant patients worldwide. However, the use of animal models in the development of these drugs is not perfect, and this has brought to light a number of issues including idiosyncratic reactions that are found in animal models but not in humans. Read More

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http://dx.doi.org/10.1080/17460441.2018.1535589DOI Listing
November 2018

Yeast: bridging the gap between phenotypic and biochemical assays for high-throughput screening.

Authors:
Paul W Denny

Expert Opin Drug Discov 2018 Oct 16:1-8. Epub 2018 Oct 16.

a Department of Biosciences and Centre for Global Infectious Disease , Durham University , Durham , UK.

Introduction: Both in vitro biochemical and phenotypic assay platforms have clear limitations in high throughput screening (HTS) for drug discovery. The use of genetically tractable model yeast as a vehicle for target-based HTS overcomes many of these by allowing the identification of on-target compounds that function within a eukaryotic cellular context. Areas covered: In this special report, the use of yeast-based assays in HTS is discussed with reference to the various platforms that have been utilized over the past 20 years. Read More

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http://dx.doi.org/10.1080/17460441.2018.1534826DOI Listing
October 2018

Testing for drug-human serum albumin binding using fluorescent probes and other methods.

Expert Opin Drug Discov 2018 Nov 15;13(11):1005-1014. Epub 2018 Oct 15.

a National Center for Advancing Translational Sciences , National Institutes of Health , Rockville , Maryland , USA.

Introduction: Drug plasma protein binding remains highly relevant to research and drug development, making the assessment and profiling of compound affinity to plasma proteins essential to drug discovery efforts. Although there are a number of fully-characterized methods, they lack the throughput to handle large numbers of compounds. As the evaluation of adsorption, distribution, metabolism, and excretion is addressed earlier in the drug development timeline, the need for higher-throughput methods has grown. Read More

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http://dx.doi.org/10.1080/17460441.2018.1534824DOI Listing
November 2018
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High-throughput drug screens for amyotrophic lateral sclerosis drug discovery.

Expert Opin Drug Discov 2018 Nov 13;13(11):1015-1025. Epub 2018 Oct 13.

a Sheffield Institute for Translational Neuroscience (SITraN) , University of Sheffield , Sheffield , United Kingdom.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapid adult-onset neurodegenerative disorder characterised by the progressive loss of upper and lower motor neurons. Current treatment options are limited for ALS, with very modest effects on survival. Therefore, there is a unmet need for novel therapeutics to treat ALS. Read More

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http://dx.doi.org/10.1080/17460441.2018.1533953DOI Listing
November 2018
2 Reads

Opportunities and challenges with animal models for acute radiation syndrome drug discovery.

Expert Opin Drug Discov 2018 Nov 29;13(11):987-992. Epub 2018 Sep 29.

c Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA.

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https://www.tandfonline.com/doi/full/10.1080/17460441.2018.1
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http://dx.doi.org/10.1080/17460441.2018.1526172DOI Listing
November 2018
16 Reads
3.470 Impact Factor

Small animal models of filovirus disease: recent advances and future directions.

Expert Opin Drug Discov 2018 Nov 29;13(11):1027-1040. Epub 2018 Sep 29.

a Galveston National Laboratory , The University of Texas Medical Branch , Galveston , TX , USA.

Introduction: Small animal models have played a critical role in understanding the pathogenesis and transmission of disease caused by filoviruses. Notably, small animals have served to identify and validate many different approaches to countering infection with these highly pathogenic viruses. Nonetheless, predictive efficacy between each model does not appear to be equivalent as higher order animals seem to be more prognostic and therefore successful in the evaluation of medical countermeasures (MCM). Read More

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http://dx.doi.org/10.1080/17460441.2018.1527827DOI Listing
November 2018
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Fluorescent probes for G-protein-coupled receptor drug discovery.

Expert Opin Drug Discov 2018 Oct 24;13(10):933-947. Epub 2018 Sep 24.

a Center for Drug Discovery and Department of Pharmaceutical Sciences , Northeastern University , Boston , Massachusetts , USA.

Introduction: G-protein-coupled receptors (GPCRs) mediate the effects of approximately 33% of all marketed drugs. The development of tools to study GPCR pharmacology is urgently needed as it can lead to the discovery of safer and more effective medications. Fluorescent GPCR ligands represent highly sensitive and safe small-molecule tools for real-time exploration of the life of the receptor, cellular signaling, and ligand-/receptor-receptor interactions in cellulo and/or in vivo. Read More

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https://www.tandfonline.com/doi/full/10.1080/17460441.2018.1
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http://dx.doi.org/10.1080/17460441.2018.1518975DOI Listing
October 2018
5 Reads

How promising is neuroactive steroid drug discovery?

Expert Opin Drug Discov 2018 Nov 17;13(11):993-995. Epub 2018 Sep 17.

a Department of Health Sciences and Public Health , University of Cagliari , Cagliari , Italy.

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http://dx.doi.org/10.1080/17460441.2018.1518974DOI Listing
November 2018
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Drug discovery strategies and the preclinical development of D-amino-acid oxidase inhibitors as antipsychotic therapies.

Expert Opin Drug Discov 2018 Oct 22;13(10):973-982. Epub 2018 Sep 22.

a Medicinal Chemistry Research Group, Research Centre for Natural Sciences , Hungarian Academy of Sciences , Budapest , Hungary.

Introduction: D-amino-acid oxidase (DAAO) degrades D-serine, a co-agonist of the NMDA receptor whose dysfunction is involved in the positive, negative, and cognitive symptoms of schizophrenia. The inhibition of DAAO appears to be a viable strategy to increase D-serine level and to have therapeutic potential in schizophrenia. Areas covered: This review describes the efforts to develop DAAO inhibitors and to optimize their in vitro and in vivo effects in preclinical settings. Read More

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http://dx.doi.org/10.1080/17460441.2018.1524459DOI Listing
October 2018
5 Reads

Chronic orofacial pain animal models - progress and challenges.

Expert Opin Drug Discov 2018 Oct 4;13(10):949-964. Epub 2018 Oct 4.

a Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology , Federal University of Sergipe , São Cristóvão , Brazil.

Introduction: Chronic orofacial pain is one of the most common pain conditions experienced by adults. Animal models are often selected as the most useful scientific methodology to explore the pathophysiology of the disorders that cause this disabling pain to facilitate the development of new treatments. The creation of new models or the improvement of existing ones is essential for finding new ways to approach the complex neurobiology of this type of pain. Read More

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https://www.tandfonline.com/doi/full/10.1080/17460441.2018.1
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http://dx.doi.org/10.1080/17460441.2018.1524458DOI Listing
October 2018
10 Reads