Abstract:
:With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to have in bone tissue physiopathology, exploring their potential has recently garnered increased interest. In this review, we first describe the involvement of miRNAs in bone metabolism, and then focus on their potential therapeutic applications (as bone biomarkers and molecular targets). We also highlight the as yet unsolved biological (i.e., off-target effects) and technological (i.e., specific delivering) challenges associated with their use.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Scimeca JC,Verron Edoi
10.1016/j.drudis.2017.04.007subject
Has Abstractpub_date
2017-07-01 00:00:00pages
1084-1091issue
7eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30178-2journal_volume
22pub_type
杂志文章,评审abstract::Skin is a vital protective organ, the main role of which is to provide a physical barrier and to prevent the entry of pathogens. Various pathologies, such as atopic dermatitis (AD), psoriasis (PSO), or skin cancers, can affect the skin, and all show a high and increasing prevalence. Many antibodies are currently used ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.10.023
更新日期:2021-01-01 00:00:00
abstract::Following multiple warnings from governments and health organisations, there has been renewed investment, led by the public sector, in the discovery of novel antimicrobials to meet the challenge of rising levels of drug-resistant infection, particularly in the case of resistance to antibiotics. Initiatives have also b...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.11.015
更新日期:2019-02-01 00:00:00
abstract::Denosumab (Dmab) was the first monoclonal antibody (mAb) approved for the treatment of osteoporosis. It blocks the receptor activator for nuclear factor κB ligand (RANKL) and acts as a potent antiresorptive agent. In contrast to classic antiresorptive agents, Dmab treatment leads to a progressive increase in bone mass...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.09.001
更新日期:2020-09-09 00:00:00
abstract::Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.01.019
更新日期:2012-03-01 00:00:00
abstract::Medical oncologists are increasingly using anti-angiogenic drugs, but identifying the best-suited drug and the optimal dosage and schedule for treatment of patients remain challenging issues. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are modulated in a variety of diseases incl...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.08.011
更新日期:2007-10-01 00:00:00
abstract::Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in the USA. Recent experimental and theoretical studies suggest that VF could be caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves has been linked to electrical alternans, a phenome...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02567-9
更新日期:2003-02-15 00:00:00
abstract::Cancer is the second highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small molecule inhibitors and nanotherapeutics have been employed in battling cancer. Amongst them, nanotheranostics is an example of successful personalized medicine bearing dual ro...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.08.009
更新日期:2019-02-01 00:00:00
abstract::Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for pa...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.10.013
更新日期:2018-05-01 00:00:00
abstract::In recent years there has been a dramatic increase in the number of freely accessible online databases serving the chemistry community. The internet provides chemistry data that can be used for data-mining, for computer models, and integration into systems to aid drug discovery. There is however a responsibility to en...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.02.013
更新日期:2012-07-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)01831-1
更新日期:2001-07-01 00:00:00
abstract::The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, unc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.11.025
更新日期:2020-11-27 00:00:00
abstract::Epigenetic covalent modifications of DNA and chromatin proteins strongly affect gene expression and cellular activity, and epigenetic misregulation occurs in several diseases, especially cancer. First-generation drugs targeting the relatively promiscuous DNA methylation and histone acetylation modifiers have had succe...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.10.010
更新日期:2010-01-01 00:00:00
abstract::Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects ac...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.05.005
更新日期:2015-09-01 00:00:00
abstract::Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03489-6
更新日期:2005-07-01 00:00:00
abstract::The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a pote...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02562-x
更新日期:2003-01-15 00:00:00
abstract::Here, we describe a novel workflow combining informatic and experimental approaches to enable evidence-based prioritising of targets from large sets in parallel. High-throughput protein production and biophysical fragment screening is used to identify those targets that are tractable and ligandable. As proof of concep...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.09.003
更新日期:2020-09-10 00:00:00
abstract::The musculoskeletal system is an incredible machine that protects, supports and moves the human body. However, several diseases can limit its functionality, compromising patient quality of life. Designing novel pathological models would help to clarify the mechanisms driving such diseases, identify new biomarkers and ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.04.015
更新日期:2016-09-01 00:00:00
abstract::Identification and validation of viable targets is an important first step in drug discovery and new methods, and integrated approaches are continuously explored to improve the discovery rate and exploration of new drug targets. An in silico machine learning method, support vector machines, has been explored as a new ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.02.015
更新日期:2007-04-01 00:00:00
abstract::Research consortia in Europe often compete with each other for skills, human and technical resources and, eventually, recognition of the scientific impact of their work. In response to the same EU Horizon2020 call, we received funding for our research project proposals to identify and validate novel drug targets for c...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.01.009
更新日期:2020-04-01 00:00:00
abstract::Various animal models are used to study pharmacokinetics (PK) of drugs in development. Human renal clearance (CLr) should be predictable through interpolation from animal data by allometric scaling. Based on this premise, we quantified interspecies differences in CLr, and related them to drug properties. Using PubMed ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.01.018
更新日期:2020-04-01 00:00:00
abstract::Effective direct inhibition of adhesion receptors by small molecules has been hampered by extended receptor-ligand interfaces as well as the entropic penalties often associated with inhibition of cell adhesion. Therefore, alternative strategies have targeted enzymes that are centrally involved in the biosynthesis of r...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01581-6
更新日期:2001-01-01 00:00:00
abstract::Covalent allosteric modulators possess the pharmacological advantages (high potency, extended duration of action and low drug resistance) of covalent ligands and the additional benefit of the higher specificity and lower toxicity of allosteric modulators. This approach is gaining increasing recognition as a valuable t...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters. 3D structures for the ligand-binding domain (LBD) of these receptors are abundantl...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.01.001
更新日期:2013-06-01 00:00:00
abstract::The sustained growth of biotechnology in North Carolina has made the state a worldwide leader in biotechnology. ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/S1359-6446(05)03650-0
更新日期:2005-11-15 00:00:00
abstract::The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry. The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive ch...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.11.010
更新日期:2013-04-01 00:00:00
abstract::Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of th...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03277-5
更新日期:2005-01-01 00:00:00
abstract::There is an urgent need for fresh approaches to the treatment of bacterial infections because of the changing patterns of infectious disease and the emergence of bacterial strains resistant to current antibiotics. Modification of the cell phenotype to sensitize bacteria to components of the hosts' immune system or to ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02498-4
更新日期:2002-11-01 00:00:00
abstract::The sequencing of the human genome and numerous pathogen genomes has resulted in an explosion of potential drug targets. These targets represent both an unprecedented opportunity and a technological challenge for the pharmaceutical industry. A new strategy is required to initiate small-molecule drug discovery with set...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01468-9
更新日期:2000-04-01 00:00:00
abstract::Polymer-drug conjugates (PDC) have exhibited clinical and commercial success in the field of drug delivery. A polymeric backbone, linker, targeting moiety, and drug constitute the building blocks of PDCs. Current attention is focusing on natural polymeric carriers, in particular the concept of graft copolymers, such a...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.06.028
更新日期:2020-09-01 00:00:00
abstract::Implementation of pragmatic design elements in drug development could bridge the evidence gap that currently exists between the knowledge we have regarding the efficacy of a drug versus its true, comparative effectiveness in real life. We performed a review of the literature to identify the ethical challenges thus far...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.03.005
更新日期:2015-07-01 00:00:00