Abstract:
:Natural products, or their synthetic derivatives are a treasure trove to find potential candidates for novel drugs for human treatment. The selection of diamonds from the huge pile of worthless stone is a critical--and difficult--stage in the discovery pipeline. Of all the factors to be considered, perhaps the most important, is that the compound should have the desired effect on the tissue in vivo. Since it is not possible (or ethical) to test all compounds in vivo one must preselect using a surrogate assay system. While animal models have the advantage of being holistic and current 3D culture systems are reductionistic, they at least can be constructed from human cell types. In this review we will consider some of the evidence demonstrating that cells grown in 3D cultures have physiological performances that mimic functions seen in human tissues significantly better than cells grown using classical 2D culture systems. We will discuss advantages and disadvantages of these new culture technologies and highlight theoretical reasons for the differences. 3D cell culture technologies are more labour intensive than 2D culture systems and therefore their introduction is a trade-off between the value of obtaining data that is more relevant to the human condition against their through-put. It is already clear that future in vitro 3D systems will become more complex, using multiple cell types to more faithfully represent a particular tissue or even organ system. And one thing is sure - the diamonds are not easy to find!
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Wrzesinski K,Fey SJdoi
10.2174/1381612821666151002114227subject
Has Abstractpub_date
2015-01-01 00:00:00pages
5605-16issue
38eissn
1381-6128issn
1873-4286pii
CPD-EPUB-70843journal_volume
21pub_type
杂志文章,评审abstract::Multiple Sclerosis (MS) is the most common autoimmune demyelinating disorder in Western countries and can lead to permanent disability. Over the past decades remarkable progress has been made in providing new therapeutic strategies to tackle the burden of the disease. Oral drugs and monoclonal antibodies are the main ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798157630
更新日期:2011-01-01 00:00:00
abstract::We estimated the frequency of detection of different human papillomavirus (HPV) types in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology in a population-based primary screening programme. 247 liquid-based cytology (LBC) samples with A...
journal_title:Current pharmaceutical design
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doi:
更新日期:2013-01-01 00:00:00
abstract::The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190304123545
更新日期:2019-01-01 00:00:00
abstract::The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying disea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795703753
更新日期:2011-01-01 00:00:00
abstract::Naturally occurring abietane diterpenoids have been studied over the years and have shown to display a wide range of biological activities. This review covers three main aspects of the abietane-type diterpenoids with hydroxy-p-quinone C ring, designated as royleanones. An overview of 1) the naturally occurrence, 2) ch...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151211094521
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Tissue engineering (TE) is a promising solution for orthopaedic diseases such as bone or cartilage defects and bone metastasis. Cell culture in vitro and scaffold fabrication are two main parts of TE, but these two methods both have their own limitations. The static cell culture medium is unable to achieve m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190301142833
更新日期:2018-01-01 00:00:00
abstract::The vasoconstrictive and antidiuretic physiologic properties of vasopressin (antidiuretic hormone) have long been known. Until recently however, vasopressin was mostly used for diabetes insipidus and noctournal enuresis. This review summarizes the growing body of evidence regarding the perioperative use of vasopressin...
journal_title:Current pharmaceutical design
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doi:10.2174/138161212803832326
更新日期:2012-01-01 00:00:00
abstract::The Hereditary Spastic Paraparesis (HSP) or Strumpell-Lorrain disease is a heterogeneous neurodegenerative disease of the spinal cord. It is genetically transmitted and characterized by a progressive muscle weakness, spasticity of the lower limbs and awkward gain. There is no specific pharmacological treatment. The ph...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666151204001830
更新日期:2016-01-01 00:00:00
abstract::Aspirin is the cornerstone of treatment in patients with coronary artery disease. However, several studies investigating the in vitro response of platelets to the administration of aspirin showed this response to be variable, with some patients exhibiting non-responsiveness or resistance. Aspirin resistance may be cat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787846964
更新日期:2009-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common form of dementia in the elderly. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit, but unfortunately, it has been only successful in terms of developing symptomatic treatments. Aβ deposition a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150914121149
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Enhancing a compound's biological activity is the central task for lead optimization in small molecules drug discovery. However, it is laborious to perform many iterative rounds of compound synthesis and bioactivity tests. To address the issue, it is highly demanding to develop high quality in silico bioacti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200427111309
更新日期:2020-01-01 00:00:00
abstract::This review describes gene therapy strategies that take advantage of defective signal transduction pathways to selectively kill cancer cells without adversely affecting normal cells. The distinctive features of cancer cells currently exploited by gene therapy include mitosis, cell permissiveness to infection, specific...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393927
更新日期:2002-01-01 00:00:00
abstract::Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are used to treat several diseases including hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from food, particularly from fatty fish. This review presents the literature examining the differences ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789909665
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The failing heart is characterized by a depleted metabolic energy reserve and the upregulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. OBJ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170321094711
更新日期:2017-01-01 00:00:00
abstract::Marine fungi with their successful pharmacological effects were considered to be the treasure of ocean medicines concerning the striking ability of their secondary metabolites. Literature over literature has been published on fungi derived bioactive molecules to probe its therapeutic potential. Marine fungi have an im...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200728142244
更新日期:2020-07-28 00:00:00
abstract::Metal ions that leach into biotherapeutic drug product solution during manufacturing and storage, result in contamination that can cause physico-chemical degradation of the active molecule. In this review, we describe various mechanisms by which metal ion leachates can interact with therapeutic proteins and antibodies...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990063
更新日期:2014-01-01 00:00:00
abstract::The complex system of molecular communications underlying cell biochemistry and function involves numerous components including kinases, phosphatases and transcription factors, which are known to be sensitive to cellular and tissue redox changes. Reactive oxygen species (ROS), whose constitutive generation in cells an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798764906
更新日期:2011-12-01 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151124234417
更新日期:2016-01-01 00:00:00
abstract::Supraventricular tachycardias (SVTs) are observed in 0,1-0,4% of the paediatric population and represent an important clinical problem with related significant health and social issues. Most tachycardias are paroxysmal, being associated with sudden onset and termination, and only a relatively small number of them is p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784007761
更新日期:2008-01-01 00:00:00
abstract::Since ancient times the operation of the brain has elicited more than usual interest. Data mining of the human genome is revealing that many CNS abnormalities have a genetic component. As yet this information can not be used directly to cure or ameliorate specific CNS disorders although this is regarded as having grea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394250
更新日期:2002-01-01 00:00:00
abstract::Somatostatin is a tetradeca peptide hormone produced by many different endocrine cells throughout the body. It is also present in both the central and peripheral nervous system. The peptide has many different moods of action including inhibition of hormone secretion and influence on gastrointestinal motility. Somatost...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
abstract::Senescence is defined as an irreversible growth arrest that is characterised by a changed morphology, gene expression pattern and chromatin structure as well as an activated DNA damage response. Senescence has a dual role for tumour development-it acts as a tumour suppressor to prevent the proliferation of seriously d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210789941874
更新日期:2010-01-01 00:00:00
abstract::The prevalence of fungal infections of skin has increased rapidly, affecting approximately 40 million people across the globe. A wide variety of antifungal drugs has been utilized in the effective management of numerous dermatological infections. Topical treatment of fungal infections has proved to be quite advantageo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150428150456
更新日期:2015-01-01 00:00:00
abstract::Most heterosexual women want to reduce the risk of acquiring a sexually transmitted infection; many also want to control their fertility. Several chemical agents have been proposed to dramatically slow the spread of HIV infections. Ideally, vaginal microbicides, with or without contraceptive properties, should be safe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774580705
更新日期:2005-01-01 00:00:00
abstract::In recent years, our understanding of the molecular interaction of collagens with their cognate integrin receptors has remarkably improved. Structural elucidations of both the integrin and the collagenous triple helix have contributed to this achievement. The structures of an entire integrin ectodomain and of an A-dom...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381738
更新日期:2005-01-01 00:00:00
abstract::Atrial fibrillation (AF) is a frequent cardiac arrhythmia. It is a common major cause of serious diseases and is an increasing health-care burden. AF is associated with an excess amount of reactive oxygen species. In this review, we summarize several possible reactive oxygen species pathways that induce AF based on at...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180903144042
更新日期:2018-01-01 00:00:00
abstract::This review describes recent advances in the development of DNA-photocleavage agents. Major mechanisms of photosensitized DNA photocleavage are presented and the most popular categories of compounds are considered, which include metal complexes and many organic functional derivatives. DNA-targeted conjugates of photos...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397140
更新日期:2001-11-01 00:00:00
abstract::In recent years, there has been an exciting focus of research attempting to understand neuropsychiatric disorders from a holistic perspective in order to determine the role of gut microbiota in the aetiology and pathogenesis of such disorders. Thus, the possible therapeutic benefits of targeting gut microbiota are bei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200122153541
更新日期:2020-01-01 00:00:00
abstract::Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507477
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, a leading cause of death and disability in developed countries. Therapeutic options are notably limited. There is no specific pharmacological treatment, and early surgery has few indications that represent only a small clinically relevant s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161221153937
更新日期:2017-01-01 00:00:00