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














  • Revival of the regulatory T cell: new targets for drug development.

    abstract::Compelling new evidence supports the idea that regulatory T cells play a major role in our immune system. Several subsets of these regulators have been identified recently. Differences in the phenotypical and functional characteristics of these subsets have immunological implications. From our growing knowledge of the...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Sutmuller RP,Offringa R,Melief CJ

    更新日期:2004-04-01 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

  • Surrogate approaches in development of monoclonal antibodies.

    abstract::When cross-reactivity of a lead antibody across species is limited, antibody development programs require the generation of surrogate molecules or surrogate animal models necessary for the conduct of preclinical pharmacology and safety studies. When surrogate approaches are employed, the complexities and challenges fo...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Bornstein GG,Klakamp SL,Andrews L,Boyle WJ,Tabrizi M

    更新日期:2009-12-01 00:00:00

  • Targeting PRAS40 for multiple diseases.

    abstract::Proline-rich Akt substrate 40kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Chong ZZ

    更新日期:2016-08-01 00:00:00

  • Accelerating biomedical innovation: a case study of the SPARK program at Stanford University, School of Medicine.

    abstract::Translating academic medical research into new therapies is an important challenge for the biopharmaceutical industry and investment communities, which have historically favored later-stage assets with lower risk and clearer commercial value. The Stanford SPARK program is an innovative model for addressing this challe...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Kim ES,Omura PMC,Lo AW

    更新日期:2017-07-01 00:00:00

  • Recent developments in natural product-based drug discovery for tuberculosis.

    abstract::Natural products (NPs) have been at the origin of several established drugs against tuberculosis (TB). Although the current clinical TB pipeline does not feature any candidates derived from new NP scaffolds, numerous novel NPs or NP analogs have been discovered in the recent past with promising activity against Mycoba...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Dong M,Pfeiffer B,Altmann KH

    更新日期:2017-03-01 00:00:00

  • Strategies for brain-targeting liposomal delivery of small hydrophobic molecules in the treatment of neurodegenerative diseases.

    abstract::Neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), threaten the health of an ever-growing number of older people worldwide; so far, there are no effective cures. Significant efforts have been devoted to developing new drugs for NDs in recent years, and some small molecul...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Wang ZY,Sreenivasmurthy SG,Song JX,Liu JY,Li M

    更新日期:2019-02-01 00:00:00

  • Mining the GEMS--a novel platform technology targeting post-transcriptional control mechanisms.

    abstract::The physiological levels of many clinically important proteins are regulated through cellular mechanisms that control the stability and translational efficiency of mRNA. These post-transcriptional processes, which play a critical role in the regulation of gene expression, depend on interactions of specific trans-actin...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Bhattacharyya A,Trotta CR,Peltz SW

    更新日期:2007-07-01 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

  • Impact of new technologies for cellular screening along the drug value chain.

    abstract::High-information screening formats, using more physiologically relevant cellular models and readout approaches, are slowly replacing traditional, target-orientated approaches in drug discovery programs. With improved access to primary cells, as well as label-free, non-intrusive methods of compound interrogation (such ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Möller C,Slack M

    更新日期:2010-05-01 00:00:00

  • Indacaterol/glycopyrronium: a dual bronchodilator for COPD.

    abstract::Indacaterol/glycopyrronium (IND/GLY) 110/50mcg was the first once-daily, long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). Development of IND/GLY was driven by the need to improve the...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Banerji D,Fogel R,Patalano F

    更新日期:2018-01-01 00:00:00

  • Cancer cell senescence: a new frontier in drug development.

    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


    authors: Cairney CJ,Bilsland AE,Evans TR,Roffey J,Bennett DC,Narita M,Torrance CJ,Keith WN

    更新日期:2012-03-01 00:00:00

  • KDI tripeptide from laminin: a novel approach to treat neurodegenerative disorders.

    abstract::The excessive release of glutamate following brain injury is responsible for the phenomenon of glutamate excitotoxicity, mediated through glutamate receptors, resulting in apoptotic cell death. KDI ameliorates excitotoxicity and regenerates damaged nerve cells. ...

    journal_title:Drug discovery today

    pub_type: 新闻


    authors: Carney S

    更新日期:2005-10-01 00:00:00

  • Support vector machines approach for predicting druggable proteins: recent progress in its exploration and investigation of its usefulness.

    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


    authors: Han LY,Zheng CJ,Xie B,Jia J,Ma XH,Zhu F,Lin HH,Chen X,Chen YZ

    更新日期:2007-04-01 00:00:00

  • Drug discovery technologies to identify and characterize modulators of the pregnane X receptor and the constitutive androstane receptor.

    abstract::The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the exp...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Chai SC,Lin W,Li Y,Chen T

    更新日期:2019-03-01 00:00:00

  • Statin-associated myopathy and the quest for biomarkers: can we effectively predict statin-associated muscle symptoms?

    abstract::Over the past three decades, statins have become the cornerstone of prevention and treatment of atherosclerotic cardiovascular and metabolic diseases. Albeit generally well tolerated, these drugs can elicit a variety of muscle-associated symptoms that represent the most important reason for treatment discontinuation. ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Muntean DM,Thompson PD,Catapano AL,Stasiolek M,Fabis J,Muntner P,Serban MC,Banach M

    更新日期:2017-01-01 00:00:00

  • Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses.

    abstract::Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Barbosa MD,Celis E

    更新日期:2007-08-01 00:00:00

  • Organometallic compounds in oncology: implications of novel organotins as antitumor agents.

    abstract::Since the introduction of cisplatin in cancer therapy, metal complexes and organometallic compounds have been gaining growing importance in oncology. The impressive clinical effectiveness of cisplatin is limited by significant side effects and the emergence of drug resistance. Thus, novel classic and unconventional Pt...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Alama A,Tasso B,Novelli F,Sparatore F

    更新日期:2009-05-01 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

  • How do we measure pathology in PAH (lung and RV) and what does it tell us about the disease.

    abstract::The current understanding of the pathology that underlies pulmonary vascular and right ventricular remodeling in pulmonary hypertension is discussed. Although recent studies underscored the importance of intima and media remodeling and, for the first time, the relevance of perivascular inflammation, much is needed to ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Tuder RM

    更新日期:2014-08-01 00:00:00

  • The development of molecular clamps as drugs.

    abstract::Some enzymes catalyze the modification of an ensemble of substrates in vivo and, as a consequence, are not ideal targets for active-site-directed drugs. One solution to inhibiting such multisubstrate enzymes would be a drug that binds tightly to only one substrate, which prevents the binding of that substrate to the e...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Weiss ST,McIntyre NR,McLaughlin ML,Merkler DJ

    更新日期:2006-09-01 00:00:00

  • Finding hidden treasures in old drugs: the challenges and importance of licensing generics.

    abstract::Identifying new indications for existing drugs creates new therapeutic options while bypassing much of the costs and time involved with bringing a new drug to market. The rediscovery of a generic drug, however, is a challenging pursuit because there is no formal regulatory approach and a lack of economic interest by p...

    journal_title:Drug discovery today

    pub_type: 杂志文章


    authors: Simsek M,Meijer B,van Bodegraven AA,de Boer NKH,Mulder CJJ

    更新日期:2018-01-01 00:00:00

  • Respiratory syncytial virus: recent progress towards the discovery of effective prophylactic and therapeutic agents.

    abstract::Although respiratory syncytial virus (RSV) was discovered in 1955, the burden associated with this infectious agent on all population groups is only now beginning to be fully appreciated. The successful launch of the humanized monoclonal antibody Synagis (developed by MedImmune, Gaithersburg, MD, USA), as a prophylact...

    journal_title:Drug discovery today

    pub_type: 杂志文章


    authors: Meanwell NA,Krystal M

    更新日期:2000-06-01 00:00:00

  • Animal venoms: therapeutic tools for tackling Parkinson's disease.

    abstract::Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: de Oliveira Amaral H,Monge-Fuentes V,Biolchi Mayer A,Alves Campos GA,Soares Lopes K,Camargo LC,Ferroni Schwartz M,Galante P,Mortari MR

    更新日期:2019-11-01 00:00:00

  • Acceleration of rare disease therapeutic development: a case study of AGIL-AADC.

    abstract::Rare-disease drug development is both scientifically and commercially challenging. This case study highlights Agilis Biotherapeutics (Agilis), a small private biotechnology company that has developed the most clinically advanced adeno-associated virus (AAV) gene therapy for the brain. In an international collaboration...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Das S,Huang S,Lo AW

    更新日期:2019-03-01 00:00:00

  • In silico platform for xenobiotics ADME-T pharmacological properties modeling and prediction. Part II: The body in a Hilbertian space.

    abstract::We have broken old surviving dogmas and concepts used in computational chemistry and created an efficient in silico ADME-T pharmacological properties modeling and prediction toolbox for any xenobiotic. With the help of an innovative and pragmatic approach combining various in silico techniques, like molecular modeling...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Jacob A,Pratuangdejkul J,Buffet S,Launay JM,Manivet P

    更新日期:2009-04-01 00:00:00

  • Hybrid poly(lactic-co-glycolic acid) nanoparticles: design and delivery prospectives.

    abstract::Poly(lactic-co-glycolic acid) (PLGA), a US Food and Drug Administration (FDA)-approved copolymer, has been exploited widely in the design of nanoparticles because it is biodegradable, biocompatible, protects the drug molecules from degradation, and aids in producing sustained and targeted delivery. However, certain co...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Pandita D,Kumar S,Lather V

    更新日期:2015-01-01 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

  • A quality alert and call for improved curation of public chemistry databases.

    abstract::In the last ten years, public online databases have rapidly become trusted valuable resources upon which researchers rely for their chemical structures and data for use in cheminformatics, bioinformatics, systems biology, translational medicine and now drug repositioning or repurposing efforts. Their utility depends o...

    journal_title:Drug discovery today

    pub_type: 社论


    authors: Williams AJ,Ekins S

    更新日期:2011-09-01 00:00:00

  • Supramolecular devices to improve the treatment of brain diseases.

    abstract::The blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Paolino D,Cosco D,Molinaro R,Celia C,Fresta M

    更新日期:2011-04-01 00:00:00