Advances in the computational development of DNA methyltransferase inhibitors.


: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.


Drug Discov Today


Drug discovery today


Medina-Franco JL,Caulfield T




Has Abstract


2011-05-01 00:00:00














  • Cancer therapy via modulation of micro RNA levels: a promising future.

    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


    authors: Kota SK,Balasubramanian S

    更新日期:2010-09-01 00:00:00

  • Chronic autoimmune-mediated inflammation: a senescent immune response to injury.

    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


    authors: 't Hart BA,Chalan P,Koopman G,Boots AM

    更新日期:2013-04-01 00:00:00

  • Application of mesoporous silica nanoparticles as drug delivery carriers for chemotherapeutic agents.

    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


    authors: Alyassin Y,Sayed EG,Mehta P,Ruparelia K,Arshad MS,Rasekh M,Shepherd J,Kucuk I,Wilson PB,Singh N,Chang MW,Fatouros DG,Ahmad Z

    更新日期:2020-08-01 00:00:00

  • Molecular and cellular biomarkers for angiogenesis in clinical oncology.

    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


    authors: Bertolini F,Mancuso P,Shaked Y,Kerbel RS

    更新日期:2007-10-01 00:00:00

  • The MEK5/ERK5 signalling pathway in cancer: a promising novel therapeutic target.

    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


    authors: Simões AE,Rodrigues CM,Borralho PM

    更新日期:2016-10-01 00:00:00

  • Interaction of tumor cells with the immune system: implications for dendritic cell therapy and cancer progression.

    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


    authors: Imhof M,Karas I,Gomez I,Eger A,Imhof M

    更新日期:2013-01-01 00:00:00

  • Epigenetic opportunities and challenges in cancer.

    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


    authors: Best JD,Carey N

    更新日期:2010-01-01 00:00:00

  • Computational systems biology approaches to anti-angiogenic cancer therapeutics.

    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


    authors: Finley SD,Chu LH,Popel AS

    更新日期:2015-02-01 00:00:00

  • New perspectives in oral peptide delivery.

    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


    authors: Zizzari AT,Pliatsika D,Gall FM,Fischer T,Riedl R

    更新日期:2021-01-23 00:00:00

  • Humans are animals, but are animals human enough? A systematic review and meta-analysis on interspecies differences in renal drug clearance.

    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


    authors: Jansen K,Pou Casellas C,Groenink L,Wever KE,Masereeuw R

    更新日期:2020-04-01 00:00:00

  • Drug discovery: are productivity metrics inhibiting motivation and creativity?

    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


    authors: Ullman F,Boutellier R

    更新日期:2008-11-01 00:00:00

  • Pharmaceutical approaches to the treatment of obesity.

    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


    authors: Jandacek RJ,Woods SC

    更新日期:2004-10-15 00:00:00

  • Do enthalpy and entropy distinguish first in class from best in class?

    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


    authors: Freire E

    更新日期:2008-10-01 00:00:00

  • Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

    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


    authors: Laurencin CT,Ashe KM,Henry N,Kan HM,Lo KW

    更新日期:2014-06-01 00:00:00

  • Mistletoe compound enters clinical trials.

    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


    authors: Habeck M

    更新日期:2003-01-15 00:00:00

  • Knowledge-based chemoinformatic approaches to drug discovery.

    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


    authors: Ghose AK,Herbertz T,Salvino JM,Mallamo JP

    更新日期:2006-12-01 00:00:00

  • The promise of a virtual lab in drug discovery.

    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


    authors: Rauwerda H,Roos M,Hertzberger BO,Breit TM

    更新日期:2006-03-01 00:00:00

  • E-drug delivery: a futuristic approach.

    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


    authors: Yadav KS,Kapse-Mistry S,Peters GJ,Mayur YC

    更新日期:2019-04-01 00:00:00

  • A challenging drug development process in the era of personalized medicine.

    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


    authors: Jørgensen JT

    更新日期:2011-10-01 00:00:00

  • Graphene-based nanomaterials for drug and/or gene delivery, bioimaging, and tissue engineering.

    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


    authors: Zhao H,Ding R,Zhao X,Li Y,Qu L,Pei H,Yildirimer L,Wu Z,Zhang W

    更新日期:2017-09-01 00:00:00

  • Improvement of preclinical animal models for autoimmune-mediated disorders via reverse translation of failed therapies.

    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


    authors: 't Hart BA,Jagessar SA,Kap YS,Haanstra KG,Philippens IH,Serguera C,Langermans J,Vierboom M

    更新日期:2014-09-01 00:00:00

  • Frontal affinity chromatography with MS detection (FAC-MS) in drug discovery.

    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


    authors: Slon-Usakiewicz JJ,Ng W,Dai JR,Pasternak A,Redden PR

    更新日期:2005-03-15 00:00:00

  • Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs.

    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


    authors: van Rijt SH,Sadler PJ

    更新日期:2009-12-01 00:00:00

  • Minimizing the risk of chemically reactive metabolite formation of new drug candidates: implications for preclinical drug design.

    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


    authors: Brink A,Pähler A,Funk C,Schuler F,Schadt S

    更新日期:2017-05-01 00:00:00

  • Top 100 bestselling drugs represent an arena struggling for new FDA approvals: drug age as an efficiency indicator.

    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


    authors: Polanski J,Bogocz J,Tkocz A

    更新日期:2015-11-01 00:00:00

  • New avenues to target Wnt/β-catenin signaling.

    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


    authors: Verkaar F,Zaman GJ

    更新日期:2011-01-01 00:00:00

  • Molecular perspectives on solid-state phase transformation and chemical reactivity of drugs: metoclopramide as an example.

    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


    authors: Lin SY

    更新日期:2015-02-01 00:00:00

  • Biosynthesis, degradation and pharmacological importance of the fatty acid amides.

    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


    authors: Farrell EK,Merkler DJ

    更新日期:2008-07-01 00:00:00

  • Mammalian carboxylesterases: from drug targets to protein therapeutics.

    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


    authors: Redinbo MR,Potter PM

    更新日期:2005-03-01 00:00:00

  • The clinical benefits, ethics, and economics of stratified medicine and companion diagnostics.

    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


    authors: Trusheim MR,Berndt ER

    更新日期:2015-12-01 00:00:00