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PubMed Journals Articles About "Epigenetic Drug Discovery Systematic Assessment Chemical Space" RSS

09:00 EST 12th December 2019 | BioPortfolio

Epigenetic Drug Discovery Systematic Assessment Chemical Space PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Epigenetic Drug Discovery Systematic Assessment Chemical Space articles that have been published worldwide.

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Showing "Epigenetic drug discovery systematic assessment chemical space" PubMed Articles 1–25 of 33,000+

Epigenetic drug discovery: systematic assessment of chemical space.

The druggability of epigenetic targets has prompted researchers to develop small-molecule therapeutics. However, no systematic assessment has ever been done to investigate the chemical space of epigenetic modulators. Herein, we report a comprehensive chemoinformatic analysis of epigenetic ligands from EpiDBase, HEMD, ChEMBL and PubChem databases. Nearly, 0.45 × 10 ligands were analyzed for assay interference compounds, target profiling, drug-like properties and hit prioritization. After eliminating approx...


Reaching for the bright StARs in chemical space.

Visualization of activity data in chemical space is common in drug discovery. Navigating the space in a systematic manner is not trivial, given its size and huge coverage. To this end, methods for data visualization have been developed charting biological activity into chemical space. Herein, we review the progress in different visualization approaches to explore the chemical space aiming at reaching insightful structure-activity relationships (SARs) in the chemical space. We discuss recent methods includin...

An overview of late-stage functionalization in today's drug discovery.

: Late-stage functionalization (LSF) can introduce important chemical groups in the very last steps of the synthesis. LSF has the potential to speed up the preparation of novel chemical entities and diverse chemical libraries and have a major impact on drug discovery. Functional group tolerance and mild conditions allows access to new molecules not easily accessible by conventional approaches without the need for laborious chemical synthesis. : A historical overview of late-stage functionalization and its ...


Machine learning for target discovery in drug development.

The discovery of macromolecular targets for bioactive agents is currently a bottleneck for the informed design of chemical probes and drug leads. Typically, activity profiling against genetically manipulated cell lines or chemical proteomics is pursued to shed light on their biology and deconvolute drug-target networks. By taking advantage of the ever-growing wealth of publicly available bioactivity data, learning algorithms now provide an attractive means to generate statistically motivated research hypoth...

Chemogenomic Analysis of the Druggable Kinome and Its Application to Repositioning and Lead Identification Studies.

Owing to the intrinsic polypharmacological nature of most small-molecule kinase inhibitors, there is a need for computational models that enable systematic exploration of the chemogenomic landscape underlying druggable kinome toward more efficient kinome-profiling strategies. We implemented VirtualKinomeProfiler, an efficient computational platform that captures distinct representations of chemical similarity space of the druggable kinome for various drug discovery endeavors. By using the computational plat...

Drug Syntheses Beyond the Rule of 5.

Drugs in chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral absorption. Reviewing the syntheses of bRo5 drugs approved since 1990 highlights synthetic chemistry's contribution to drug discovery in this space. Initially, bRo5 drugs were mainly natural products and semisynthetic derivatives. Later, peptidomimetics and de novo designed compounds, that include up to seven chiral centres and macrocyclic rings became dominant. Th...

Systematic diversity-oriented synthesis of reduced flavones from γ-pyrones to probe biological performance diversity.

Diversity-oriented synthesis (DOS) has historically focused on the development of small-molecule collections with considerable chemical diversity with the hypothesis that chemical diversity will lead to diverse biological activities. We have taken a systematic approach to DOS to develop a focused library of reduced flavones from γ-pyrones with diversity of appendage, stereochemistry, and chemical properties to determine which features of small molecules are most predictive of biological performance diversi...

Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics.

Thymoquinone is a natural product known for its anticancer activity. Preclinical studies indicated numerous mechanisms of action by which thymoquinone exerts its effects on cancer cells. Recent evidence has indicated that thymoquinone can modulate epigenetic machinery, like modifying histone acetylation and deacetylation, DNA methylation and demethylation, which are among the major epigenetic changes that can contribute to carcinogenesis. Moreover, thymoquinone can alter the genetic expression of various no...

Comprehensive Real-World Assessment of Marketed Medications to Guide Parkinson's Drug Discovery.

Parkinson's disease is a disorder growing in prevalence, disability, and deaths. Healthcare databases provide a 'real-world' perspective for millions of individuals. We envisioned helping accelerate drug discovery by using these databases.

Reliability of Click Chemistry on Drug Discovery: A Personal Account.

The unprecedented efficiency, reliability and adaptability in drug discovery, with the growing number of applications and impact, have made Click Chemistry fascinating to the scientific community. The specificity, biocompatibility along with other principles of click chemistry offers a reliable platform for synthesis of drug-like molecules that can expedite the drug discovery process. This account summarizes such successes of versatile click reactions from our group towards the development of functional mol...

Interoperable chemical structure search service.

The existing connections between large databases of chemicals, proteins, metabolites and assays offer valuable resources for research in fields ranging from drug design to metabolomics. Transparent search across multiple databases provides a way to efficiently utilize these resources. To simplify such searches, many databases have adopted semantic technologies that allow interoperable querying of the datasets using SPARQL query language. However, the interoperable interfaces of the chemical databases still ...

The importance of target binding kinetics for measuring target binding affinity in drug discovery: a case study from a CRF receptor antagonist program.

In drug discovery, it is essential to accurately measure drug-target binding affinity. Here, we revisit the fact that target binding kinetics impact the measurement of affinity, using a case study: development of corticotropin-releasing factor antagonists. Slow dissociation of the drug-target complex results in affinity assays being far from equilibrium, which results in erroneous estimates of affinity. This scenario impairs prediction of human dosing, assessment of target selectivity, identification of hig...

Concepts of Artificial Intelligence for Computer-Assisted Drug Discovery.

Artificial intelligence (AI), and, in particular, deep learning as a subcategory of AI, provides opportunities for the discovery and development of innovative drugs. Various machine learning approaches have recently (re)emerged, some of which may be considered instances of domain-specific AI which have been successfully employed for drug discovery and design. This review provides a comprehensive portrayal of these machine learning techniques and of their applications in medicinal chemistry. After introducin...

The Exploration of Chirality for Improved Druggability within the Human Kinome.

Chirality is important in drug discovery since stereoselective drugs can ameliorate therapeutic difficulties including adverse toxicity and poor pharmacokinetic profiles. The human kinome, a major druggable, enzyme class has been exploited to treat a wide range of diseases. However, many kinase inhibitors are planar and overlap in chemical space, which leads to selectivity and toxicity issues. By exploring chirality within the kinome, a new iteration of kinase inhibitors is being developed to better utilize...

A multiparametric organ toxicity predictor for drug discovery.

The assessment of major organ toxicities through predictive models plays a crucial role in drug discovery. Computational tools can predict chemical toxicities using the knowledge gained from experimental studies which drastically reduces the attrition rate of compounds during drug discovery and developmental stages. The purpose of predictions for drug leads and anticipating toxicological endpoints of absorption, distribution, metabolism, excretion and toxicity, clinical adverse impacts and metabolism of p...

Epigenetics and addiction.

As an individual becomes addicted to a drug of abuse, nerve cells within the brain's reward circuitry adapt at the epigenetic level during the course of repeated drug exposure. These drug-induced epigenetic adaptations mediate enduring changes in brain function which contribute to life-long, drug-related behavioral abnormalities that define addiction. Targeting these epigenetic alterations will enhance our understanding of the biological basis of addiction and might even yield more effective anti-addiction ...

From Target to Drug: Generative Modeling for Multimodal Structure-Based Ligand Design.

Chemical space is impractically large and conventional structure-based virtual screening techniques cannot be used to simply search through the entire space to discover effective bioactive molecules. To address this shortcoming we propose a generative adversarial network to generate, rather than search, diverse three-dimensional ligand shapes complementary to the pocket. Furthermore, we show that the generated molecule shapes can be decoded using a shape-captioning network into a sequence of SMILES enabling...

Role of High-Throughput Electrophysiology in Drug Discovery.

Due to their important physiological functions, ion channels are key therapeutic targets for a variety of disorders. However, electrophysiological assessment of ion channel activity is technically challenging and has been a bottleneck in the discovery of drugs that modulate channel function. To address this issue, automated patch clamp platforms have been developed with improved throughput and broader applications. An overview of the current status of high-throughput electrophysiology and its applications i...

Sequential Assessment of Multiple Epigenetic Modifications of Cytosine in Whole Genomic DNA by Surface Plasmon Resonance.

Since the discovery of the active DNA demethylation pathway in mammals, numerous efforts have been made to distinguish epigenetic cytosine variants, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). However, the rapid discrimination of multiple epigenetic modification in DNA remains challenging because the conventional assays require the time-consuming DNA pretreatments, such as enzymatical digestion and chemical conversion. Here, we dem...

Current progress on genomics of schistosomiasis for drug discovery and diagnostics.

For number of decades, Scistosomiasis has remained the public health and economic burden in a number of countries directly impacting over 200 million people. Past 15 years have seen tremendous progress in development of high-throughput methods for targets or compounds selection that are vital to early stage schistosome drug discovery research. Genome wide approaches to analyze gene expression at the transcriptional and other 'omic level has helped immensely for gaining insight into the pathways and mechanis...

A systematic review investigating if genetic or epigenetic markers are associated with postnatal depression.

Postnatal depression (PND) is common, affects the health of the mother, the development of the infant and places a large financial burden on services. Genetic and epigenetic biomarkers for PND could potentially improve the accuracy of current antenatal screening approaches. The aim of this systematic review is to report on the evidence for an association between genetic or epigenetic factors and postnatal depression.

DNA methyltransferases: emerging targets for the discovery of inhibitors as potent anticancer drugs.

DNA methyltransferases (DNMTs) are a conserved family of cytosine methylases with crucial roles in epigenetic regulation. They have been considered as promising therapeutic targets for the epigenetic treatment of cancer. Therefore, DNMT inhibitors (DNMTis) have attracted considerable interest in recent years for the modulation of the aberrant DNA methylation pattern in a reversible way. In this review, we provide a structure-based overview of the therapeutic importance of DNMTs against different cancer type...

Acoustic mist ionization mass spectrometry (AMI-MS) as a drug discovery platform.

The expansion of label free mass spectrometry into early drug discovery was always predicted to provide improvements in data quality and depth with the potential to reduce costs but has previously been limited by throughput. There are several techniques that vary by sample introduction technology or ionization technique that try to address the challenges in this area. Areas covered: In this review, the authors describe the deployment of such a device, combining acoustic mist ionization and time-of-flight ma...

Toward Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor.

Thyroid cancer (TC) is a very common malignancy worldwide. Chief among the innovative molecular drug targets for TC are epigenetic modifications. Increased telomerase activity in cancer cells makes telomerase a novel target for epigenetic anticancer drug innovation. Recently, telomerase reverse transcriptase () gene promoter () mutations (C228T and C250T) were reported at high frequency in TC cell lines and tumor biopsies. In this study, three representative TC cell lines, mutant (TPC1), mutant / (KTC2), a...

How can molecular micro-CT imaging revolutionize drug discovery?


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