Discovery and Development of Small Molecule Epigenetic Drugs and Probes

1st Edition - February 24, 2016

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  • Editor: Jose Medina-Franco
  • Paperback ISBN: 9780128028087
  • eBook ISBN: 9780128028094

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Epi-Informatics: Discovery and Development of Small Molecule Epigenetic Drugs and Probes features multidisciplinary strategies with strong computational approaches that have led to the successful discovery and/or optimization of compounds that act as modulators of epigenetic targets. This book is intended for all those using or wanting to learn more about computational methodologies in epigenetic drug discovery, including molecular modelers, informaticians, pharmaceutical scientists, and medicinal chemists. With a better understanding of different molecular modeling and cheminformatic approaches, readers can incorporate these techniques into their own drug discovery projects that may involve chemical synthesis and medium- or high-throughput screening. In addition, this book highlights the significance of epigenetic targets to the public health for molecular modelers and chemoinformatians. The goal of this reference is to stimulate ongoing multidisciplinary research and to further improve current computational methodologies and workflows in order to accelerate the discovery and development of epi-drugs and epi-probes.

Key Features

  • Focuses on the discovery of epi-drugs as candidates to be used in therapy including combined therapies
  • Describes new computational methodologies and screening assays utilizing recent and emerging novel structural data
  • Highlights the discovery, development and optimization of epi-probes, which are molecular probes that elucidate epigenetic mechanisms
  • Includes important topics such as computational-guided optimization of epi-hits, virtual screening to identify novel compounds for epigenetic targets, development and mining of epigenetic molecular databases, SAR modeling of screening data and much more


Pharmaceutical scientists, medicinal chemists, modelers and informaticians, biological scientists working with epigenetics in industry, academia, and non-for profit organizations working on drug discovery of epi-drugs, as well as graduate students in courses related to epigenetics, drug discovery and development, computer-aided drug design and cancer biology

Table of Contents

  • Chapter 1. Introduction of Epigenetic Targets in Drug Discovery and Current Status of Epi-Drugs and Epi-Probes

    • 1. Introduction

    Chapter 2. Overview of Computer-Aided Drug Design for Epigenetic Targets

    • 1. Introduction
    • 2. Ligand-Based Drug Design
    • 3. Structure-Based Drug Design
    • 4. Combining Methods
    • 5. Concluding Remarks

    Chapter 3. Structure-Guided Optimization of DNA Methyltransferase Inhibitors

    • 1. Introduction to DNA Methyltransferases
    • 2. Drug Discovery
    • 3. Further Promising Perspectives

    Chapter 4. Discovery and Development of Small Molecules Targeting Epigenetic Enzymes with Computational Methods

    • 1. Introduction
    • 2. Writer
    • 3. Readers
    • 4. Erasers
    • 5. Protein–Protein Interactions
    • 6. Future Directions

    Chapter 5. In Silico Optimization of the First DNA-Independent Mechanism-Based Inhibitor of Mammalian DNA Methyltransferase DNMT1

    • 1. Introduction
    • 2. Lead Structure for the Mechanism-Based Transition-State Analog
    • 3. Evaluation of the Proposed Lead Compound as a Mechanism-Based Inhibitor of DNMT1
    • 4. Optimization of Binding Interactions at Multiple Sites on the Lead Compound
    • 5. Binding of the Mechanism-Based Inhibitor to Different Conformations of DNMT1
    • 6. Conclusions and Future Directions
    • 7. Methodology
    • Appendix tables

    Chapter 6. Structure-Based Modeling of Histone Deacetylases Inhibitors

    • 1. Introduction
    • 2. SBDD Studies on Zn-Based HDAC Inhibitors
    • 3. SB Modeling for NAD-HDAC (Sirtuins)
    • 4. Conclusions

    Chapter 7. Searching Histone Deacetylase Inhibitors under Computational Procedures

    • 1. Introduction
    • 2. Histones
    • 3. Targeting Histones
    • 4. General Steps for Development of New Drugs
    • 5. Developing New Strategies to Get Selective Compounds on Histones
    • 6. Developing New Strategies to Multitarget Compounds Including Histones
    • 7. Conclusions

    Chapter 8. Current Development of Protein Arginine Methyltransferase Inhibitors

    • 1. Introduction
    • 2. Protein Arginine Methyltransferases
    • 3. Catalytic Activity of PRMTs
    • 4. Pharmacological Significance
    • 5. PRMT Inhibitors
    • 6. Conclusion
    • List of Acronyms and Abbreviations

    Chapter 9. Molecular Design of Compounds Targeting Histone Methyltransferases

    • 1. Introduction
    • 2. Protein Methyltransferases
    • 3. Clinicopathological Role of PKMTs
    • 4. Drug Discovery of New Epi-Drugs for Histone Methyltransferases
    • 5. Conclusions

    Chapter 10. Computational Chemical Biology of Methyllysine Histone Effectors

    • 1. Introduction
    • 2. Lysine Methylation: Chemistry and Biology
    • 3. Methyllysine Effectors
    • 4. What Role for Computational Approaches?
    • 5. Elucidation of Effector-Substrate Recognition
    • 6. Chemical Probes: Identification and Design
    • 7. Structural Mechanics of Methyllysine Signaling
    • 8. Conclusions and Perspectives

    Chapter 11. Structure-Based Design and Computational Studies of Sirtuin Inhibitors

    • 1. Introduction
    • 2. Sirtuins, Insights into Their Chemical Mechanism, Characteristic Features, and Substrates
    • 3. Crystal Structures of Sirtuins with Inhibitors and Activators
    • 4. Computational Studies of Sirtuin Modulators
    • 5. Conclusion

    Chapter 12. Drug Repurposing for Epigenetic Targets Guided by Computational Methods

    • 1. Introduction
    • 2. Drug Repurposing Strategies
    • 3. Drug Repurposing in Epigenetics
    • 4. Conclusions

    Chapter 13. Computational Structure–Activity Relationship Studies of Epigenetic Target Inhibitors

    • 1. Introduction
    • 2. Computational Methods to Study Structure–Activity Relationships
    • 3. Analyzing SARs of Epigenetic Targets Using Computational Tools
    • 4. Overcoming Selectivity Challenges in the Computational Design of Epi-Drugs
    • 5. Conclusions

    Chapter 14. Role of Nutrition in Epigenetics and Recent Advances of In Silico Studies

    • 1. Nutritional Genomics
    • 2. Diet and Health
    • 3. Diseases Related to Epigenetic Changes
    • 4. Computational Studies on Nutrigenomics and Food Chemicals

    Chapter 15. The Road Ahead of the Epi-Informatics Field

    • 1. Introduction
    • 2. Promising Computational Approaches in Epigenetic Drug Discovery
    • 3. Epi-Informatics: The Road Ahead
    • 4. Conclusions

Product details

  • No. of pages: 440
  • Language: English
  • Copyright: © Academic Press 2016
  • Published: February 24, 2016
  • Imprint: Academic Press
  • Paperback ISBN: 9780128028087
  • eBook ISBN: 9780128028094

About the Editor

Jose Medina-Franco

Dr. José Medina-Franco received a Bachelor of Science degree in chemistry from the National Autonomous University of Mexico (UNAM) in 1998. That same year, he joined Procter & Gamble in Mexico City, working in the research and development department. He received a Master of Science degree in 2002 and a Ph.D. degree in 2005, both from the UNAM. In 2005, he joined the University of Arizona as a postdoctoral fellow. Dr. Medina-Franco was named Assistant Member at the Torrey Pines Institute for Molecular Studies in Florida in August 2007. Since then, he has conducted research and academic activities at the Institute of Chemistry, UNAM and Mayo Clinic in Scottsdale. In 2014, he was named Full Time Research Professor of the Pharmacy Department, UNAM where he leads a computational group focused on the discovery and development of epi-drugs. He also serves as an Adjunct Professor at the Florida Atlantic University. Dr. Medina-Franco has more than 8 years of experience working on molecular modeling of DNMT inhibitors. He has lead one of the first research groups applying computational tools for drug discovery of epi-hits. His research group has published several research papers, reviews and book chapters focused on the development of DNMT inhibitors using computational methods. One of the major contributions of his group has been the identification of a distinct DNMT inhibitor with a novel molecular scaffold. The hit compound has been used as a starting point for optimization programs and has served as reference for virtual screening campaigns. Dr. Medina-Franco’s group has also initiated a novel computer-guided drug repurposing project.

Affiliations and Expertise

Professor, Department of Pharmacy, Universidad Nacional Autónoma de México, Mexico City, Mexico

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