Abstract:
:DNA methylation is an epigenetic change that results in the addition of a methyl group at the carbon-5 position of cytosine residues. The process is mediated by DNA methyltransferases (DNMTs), a family of enzymes for which inhibition is a promising strategy for the treatment of cancer and other diseases. Here, we review the current status of the computational studies directed to rationalize, at the molecular level, the enzymatic activity of DNMT inhibitors. We also review successful virtual screenings to identify inhibitors with novel scaffolds as well as the emerging efforts to characterize the dynamic behavior of DNMTs. Thus, computational approaches form part of multidisciplinary efforts to further advance epigenetic therapies.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Medina-Franco JL,Caulfield Tdoi
10.1016/j.drudis.2011.02.003subject
Has Abstractpub_date
2011-05-01 00:00:00pages
418-25issue
9-10eissn
1359-6446issn
1878-5832pii
S1359-6446(11)00035-3journal_volume
16pub_type
杂志文章,评审abstract::Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2010.07.003
更新日期:2010-09-01 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::Recently, remarkable efforts have focused on research towards enhancing and delivering efficacious and advanced therapeutic agents. Even though this involves significant challenges, innovative techniques and materials have been explored to overcome these. The advantageous properties of mesoporous silica nanoparticles ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.06.006
更新日期:2020-08-01 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::Conventional mitogen-activated protein kinase (MAPK) family members are among the most sought-after oncogenic effectors for the development of novel human cancer treatment strategies. MEK5/ERK5 has been the less-studied MAPK subfamily, despite its increasingly demonstrated relevance in the growth, survival, and differ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.06.010
更新日期:2016-10-01 00:00:00
abstract::There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells. Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of the...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.07.010
更新日期:2013-01-01 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::Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. An...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.09.026
更新日期:2015-02-01 00:00:00
abstract::Owing to their structural diversity, peptides are a unique source of innovative active ingredients. However, their development has been challenging because of their disadvantageous pharmacokinetic (PK) properties. Over the past decade, many attempts have been made to improve the oral bioavailability of peptide drugs. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2021.01.020
更新日期:2021-01-23 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::With a productivity gap in pharmaceutical research and development, and increased industrialization in both areas, an increased need for precise indicators of productivity has emerged. Measuring scientists' performance can impact the way the tasks are performed and the level of motivation of an individual. This is a c...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2008.06.015
更新日期:2008-11-01 00:00:00
abstract::The recent increase in pharmaceutical companies' efforts toward the treatment of obesity reflects recognition of the related health risks, the growth of knowledge about mechanisms that control energy balance, and the potential market for new compounds. The current patent literature gives a picture of the targets that ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03244-1
更新日期:2004-10-15 00:00:00
abstract::A drug molecule should bind to its target with high affinity and selectivity. Because the binding affinity is a combined function of the binding enthalpy and the binding entropy, extremely high affinity requires that both terms contribute favorably to binding. The binding enthalpy, however, is notoriously more difficu...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.07.005
更新日期:2008-10-01 00:00:00
abstract::Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potenti...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.01.012
更新日期:2014-06-01 00:00:00
abstract::A drug has entered clinical trials that contains a recombinant version of the main extract from mistletoe, adn holds promise for cancer patients. ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(02)02571-0
更新日期:2003-01-15 00:00:00
abstract::The modern drug discovery process is steadily becoming more information driven. Structural, physicochemical and ADME-Tox property profiles of reference (successful) ligands, along with structural information of their target proteins, have been extremely useful for early-stage drug discovery. Recently, databases of kno...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.10.012
更新日期:2006-12-01 00:00:00
abstract::To date, the life sciences 'omics' revolution has not lived up to the expectation of boosting the drug discovery process. The major obstacle is dealing with the volume and diversity of data generated. An enhanced-science (e-science) approach based on remote collaboration, reuse of data and methods, and supported by a ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03680-9
更新日期:2006-03-01 00:00:00
abstract::Drug delivery systems are undergoing technology changes to enhance patient comfort and compliance. Electronic drug delivery (E-drug delivery) systems are being developed to regulate drug dose delivery by easy monitoring of doses, especially in chronic and age-related diseases. E-drug delivery can monitor the correct d...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.02.005
更新日期:2019-04-01 00:00:00
abstract::After years of hesitation a larger number of pharmaceutical and biotech companies are now supporting the idea of a more individualized pharmacotherapy. The companies that are now involved in this research-demanding area will have to face several challenges. The key factor for success will be an in-depth molecular unde...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2011.09.010
更新日期:2011-10-01 00:00:00
abstract::Here, we discuss the biomedical applications of graphene-based nanomaterials (GBNs). We examine graphene and its various derivatives, including graphene, graphene oxides (GOs), reduced graphene oxides (rGOs), graphene quantum dots (GQDs), and graphene composites, and discuss their unique properties related to their bi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.002
更新日期:2017-09-01 00:00:00
abstract::The poor translational validity of autoimmune-mediated inflammatory disease (AIMID) models in inbred and specific pathogen-free (SPF) rodents underlies the high attrition of new treatments for the corresponding human disease. Experimental autoimmune encephalomyelitis (EAE) is a frequently used preclinical AIMID model....
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.03.023
更新日期:2014-09-01 00:00:00
abstract::The emergence of a relatively new technique resulting from a combination of frontal affinity chromatography coupled with MS detection (FAC-MS) has extended the capabilities of MS in drug discovery and development. Its application in a broad range of biological systems, together with its label-free operation, relativel...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03360-4
更新日期:2005-03-15 00:00:00
abstract::This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.09.003
更新日期:2009-12-01 00:00:00
abstract::Many pharmaceutical companies aim to reduce reactive metabolite formation by chemical modification at early stages of drug discovery. A practice often applied is the detection of stable trapping products of electrophilic intermediates with nucleophilic trapping reagents to guide rational structure-based drug design. T...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2016.11.018
更新日期:2017-05-01 00:00:00
abstract::We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2015.06.015
更新日期:2015-11-01 00:00:00
abstract::Wnt/β-catenin signaling is an evolutionarily conserved signaling cascade with imperative roles during development and in adult stem cell maintenance. Hyperactivation of Wnt/β-catenin drives various cancers, whereas hypoactivation underlies bone malformations and neurodegenerative disorders. Although several small mole...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2010.11.007
更新日期:2011-01-01 00:00:00
abstract::Here, I provide an overview of the solid-state characteristics, phase transformations and chemical reactions of metoclopramide hydrochloride monohydrate (MCP HCl H2O). Three unique techniques, including thermoanalytical methods, one-step simultaneous differential scanning calorimetry (DSC) and Fourier transform infrar...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.10.001
更新日期:2015-02-01 00:00:00
abstract::The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.02.006
更新日期:2008-07-01 00:00:00
abstract::Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03383-0
更新日期:2005-03-01 00:00:00
abstract::The stratified medicine companion diagnostic (CDx) cut-off decision integrates scientific, clinical, ethical, and commercial considerations, and determines its value to developers, providers, payers, and patients. Competition already sharpens these issues in oncology, and might soon do the same for emerging stratified...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.10.017
更新日期:2015-12-01 00:00:00