4.6 Article

7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1

Related references

Note: Only part of the references are listed.
Review Pharmacology & Pharmacy

Drug discovery for epigenetics targets

Geoffrey A. Holdgate et al.

Summary: This review provides an overview of the role of epigenetics in disease and the strategy of pharmacological intervention. It discusses the drug targets of epigenetics and the methods used for initial hit identification and chemical optimization. The review also highlights current challenges and future potential for epigenetics-based therapies.

DRUG DISCOVERY TODAY (2022)

Article Chemistry, Medicinal

Chemoinformatic Characterization of Synthetic Screening Libraries Focused on Epigenetic Targets

E. Alexis Flores-Padilla et al.

Summary: The importance of epigenetic drug and probe discovery is increasing, aiding in the development of therapeutic treatments and understanding underlying epigenetic mechanisms in biological processes. Through comprehensive analysis of eleven libraries focused on epigenetic targets, guidance is provided for experimental groups working with high-throughput and medium-throughput screening of epigenetic-focused libraries, and as a reference for designing novel focused epigenetic libraries.

MOLECULAR INFORMATICS (2022)

Review Biochemistry & Molecular Biology

Small molecule targeting of chromatin writers in cancer

Andrew R. Conery et al.

Summary: The approval of the first histone methyltransferase inhibitor in 2020 marks a significant milestone in the field of targeted manipulation of chromatin regulatory pathways for cancer treatment. Despite the complexity of identifying key targets for therapeutic intervention, approaches in chemical biology have played a critical role in discovering key nodes in these pathways and translating them into potential cancer therapies. This review highlights the importance of chemical probes, drug candidates, and translational strategies in maximizing the impact of epigenetic writer enzymes in cancer therapy.

NATURE CHEMICAL BIOLOGY (2022)

Article Oncology

Current paradigms in epigenetic anticancer therapeutics and future challenges

Manoj Singh et al.

Summary: Any alteration at the genetic or epigenetic level can lead to various diseases, including cancer. Drugs targeting epigenetic alterations have been developed for cancer treatment, but there are still challenges such as finding more effective and less side-effect inhibitors, as well as gaining a deeper understanding of tumor pathology.

SEMINARS IN CANCER BIOLOGY (2022)

Article Hematology

In vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor

Aidan G. Gilmartin et al.

Summary: The orally bioavailable DNMT1-selective inhibitor GSK3482364 has been discovered to have the potential to induce HbF expression, showing good tolerability in preclinical models.

HAEMATOLOGICA (2021)

Review Immunology

DNA methylation signatures of autoimmune diseases in human B lymphocytes

Moncef Zouali

Summary: This review explores the role of B lymphocytes in autoimmune diseases and the importance of DNA methylation in regulating cellular activation and differentiation programs. Additionally, epigenetic profiling of B cells in autoimmune diseases has revealed distinct differential methylation regions that could potentially differentiate patients from controls. Development of tools for editing DNA methylation in the mammalian genome holds promise for future functional studies of epigenetic regulation and translational applications.

CLINICAL IMMUNOLOGY (2021)

Article Chemistry, Medicinal

Expanding the Structural Diversity of DNA Methyltransferase Inhibitors

K. Euridice Juarez-Mercado et al.

Summary: Inhibitors of DNMT1, such as theaflavin, glyburide, and panobinostat, can be used for epigenetic drug discovery. Experimental results show a strong binding affinity between these compounds and DNMT1, supporting their potential as DNMT1 inhibitors.

PHARMACEUTICALS (2021)

Article Chemistry, Medicinal

Epigenetic Target Profiler: A Web Server to Predict Epigenetic Targets of Small Molecules

Norberto Sanchez-Cruz et al.

Summary: This work introduces a freely accessible web application called Epigenetic Target Profiler (ETP) for predicting epigenetic targets of small molecules. ETP utilizes ligand-based target prediction models to predict bioactivity profiles of compounds over 55 different epigenetic targets.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2021)

Review Chemistry, Multidisciplinary

Advances in the Exploration of the Epigenetic Relevant Chemical Space

Diana L. Prado-Romero et al.

Summary: Epigenetic drug discovery explores chemical spaces to identify hit and lead compounds, predict the activity of existing chemicals, guide compound design or optimization, and expand the epigenetic relevant chemical space. Advances in using structure-activity relationships stored in public chemogenomic databases facilitate drug discovery progress.

ACS OMEGA (2021)

Article Oncology

Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia

Melissa B. Pappalardi et al.

Summary: GSK3685032 is a potent first-in-class DNMT1-selective inhibitor that competes with the active-site loop of DNMT1 for penetration into hemi-methylated DNA. It induces robust loss of DNA methylation, transcriptional activation, and cancer cell growth inhibition in vitro. Compared with decitabine, GSK3685032 shows improved in vivo tolerability and superior tumor regression and survival in preclinical AML models.

NATURE CANCER (2021)

Review Cell Biology

Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends

Kunal Nepali et al.

Summary: Research in epigenetic drug discovery has advanced significantly, with efforts focused on developing treatment strategies and utilizing emerging technologies like PROTACS and CRISPR/Cas9. Multi-targeting scaffold assemblies have been proposed as potential alternatives to combination therapy.

JOURNAL OF BIOMEDICAL SCIENCE (2021)

Review Chemistry, Medicinal

Epigenetic polypharmacology: A new frontier for epi-drug discovery

Daniela Tomaselli et al.

MEDICINAL RESEARCH REVIEWS (2020)

Article Biochemistry & Molecular Biology

Towards the understanding of the activity of G9a inhibitors: an activity landscape and molecular modeling approach

Edgar Lopez-Lopez et al.

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN (2020)

Review Biochemistry & Molecular Biology

Two-hit wonders: The expanding universe of multitargeting epigenetic agents

Angel R. de Lera et al.

CURRENT OPINION IN CHEMICAL BIOLOGY (2020)

Article Chemistry, Physical

Scalable molecular dynamics on CPU and GPU architectures with NAMD

James C. Phillips et al.

JOURNAL OF CHEMICAL PHYSICS (2020)

Review Pharmacology & Pharmacy

Recent progress on cheminformatics approaches to epigenetic drug discovery

Zoe Sessions et al.

DRUG DISCOVERY TODAY (2020)

Review Oncology

Clinicopathologic significance of protein lysine methyltransferases in cancer

Theodore Vougiouklakis et al.

CLINICAL EPIGENETICS (2020)

Review Chemistry, Medicinal

Quinazolines as inhibitors of chromatin-associated proteins in histones

Frida S. Herrera-Vazquez et al.

MEDICINAL CHEMISTRY RESEARCH (2019)

Review Oncology

The emerging role of epigenetics in human autoimmune disorders

Roberta Mazzone et al.

CLINICAL EPIGENETICS (2019)

Review Endocrinology & Metabolism

The Epigenomics of Pituitary Adenoma

Blake M. Hauser et al.

FRONTIERS IN ENDOCRINOLOGY (2019)

Article Biochemistry & Molecular Biology

ChEMBL: towards direct deposition of bioassay data

David Mendez et al.

NUCLEIC ACIDS RESEARCH (2019)

Review Oncology

The timeline of epigenetic drug discovery: from reality to dreams

A. Ganesan et al.

CLINICAL EPIGENETICS (2019)

Review Pharmacology & Pharmacy

Insights from pharmacological similarity of epigenetic targets in epipolypharmacology

J. Jesus Naveja et al.

DRUG DISCOVERY TODAY (2018)

Review Pharmacology & Pharmacy

Inhibitors of DNA Methyltransferases From Natural Sources: A Computational Perspective

Fernanda I. Saldivar-Gonzalez et al.

FRONTIERS IN PHARMACOLOGY (2018)

Review Biochemistry & Molecular Biology

DNA methylation in human diseases

Zelin Jin et al.

GENES & DISEASES (2018)

Review Oncology

DNA methyltransferases and their roles in tumorigenesis

Wu Zhang et al.

BIOMARKER RESEARCH (2017)

Review Pharmacology & Pharmacy

Are epigenetic drugs for diabetes and obesity at our door step?

Andrix O. Arguelles et al.

DRUG DISCOVERY TODAY (2016)

Article Biochemistry & Molecular Biology

Allosteric control of mammalian DNA methyltransferases - a new regulatory paradigm

Albert Jeltsch et al.

NUCLEIC ACIDS RESEARCH (2016)

Review Pharmacology & Pharmacy

Discovery and development of DNA methyltransferase inhibitors using in silico approaches

Jose L. Medina-Franco et al.

DRUG DISCOVERY TODAY (2015)

Article Biochemistry & Molecular Biology

New Insights on the Mechanism of Quinoline-based DNA Methyltransferase Inhibitors

Christina Gros et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2015)

Editorial Material Chemistry, Medicinal

Challenges in developing novel DNA methyltransferase inhibitors for cancer therapy

Dominique Guianvarc'h et al.

FUTURE MEDICINAL CHEMISTRY (2014)

Review Clinical Neurology

DNA Modifications and Neurological Disorders

Yi-Lan Weng et al.

NEUROTHERAPEUTICS (2013)

Article Chemistry, Medicinal

Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines

Feng Liu et al.

JOURNAL OF MEDICINAL CHEMISTRY (2011)

Article Genetics & Heredity

Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss

Christopher J. Klein et al.

NATURE GENETICS (2011)

Article Biochemistry & Molecular Biology

Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8

Elmar Krieger et al.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS (2009)

Article Biochemistry & Molecular Biology

CXXC domain of human DNMT1 is essential for enzymatic activity

Mihika Pradhan et al.

BIOCHEMISTRY (2008)

Article Chemistry, Multidisciplinary

Importance of accurate charges in molecular docking: Quantum mechanical/molecular mechanical (QM/MM) approach

AE Cho et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2005)

Article Biochemistry & Molecular Biology

The Protein Data Bank

HM Berman et al.

NUCLEIC ACIDS RESEARCH (2000)