Epigenetics for Drug Discovery

✍ Scribed by Nessa Carey (ed.)

• Publisher: National Book Network International,Royal Society of Chemistry
• Year: 2015
• Tongue: English
• Leaves: 336
• Series: RSC drug discovery series
• Category: Library

✦ Synopsis

Epigenetics is one of the fastest moving fields in drug discovery, with almost every large pharmaceutical company and a substantial number of biotechnology companies targeting epigenetic processes to treat diseases ranging from cancer to Huntington’s disease and from inflammation to sickle cell anaemia.

The book is structured in three main sections. The first section introduces epigenetics and explain its importance at both a phenomenological and molecular level. The second section goes on to review how each of the big breakthroughs in drug discovery in this field have developed, with a strong emphasis on case histories. The final section highlights the ongoing challenges in creating safe and efficacious epigenetic drugs.

Written and edited by experts within the field from both industry and academia, this book provides an invaluable guide to this developing field for medicinal chemists working in academia and in the pharmaceutical industry.

✦ Table of Contents

Content: Cover
Epigenetics for Drug Discovery
Preface
Contents
Chapter 1 --
Epigenetics --
What it is and Why it Matters
1.1 Introduction
1.2 Beyond DNA: A Broad Picture of Epigenetic Mechanisms
1.3 Gene Regulation and the Impact of Chromatin Assembly
1.4 Chromatin Structure and the Basis of Epigenetic Mechanisms
1.5 Gene Regulation in Chromatin: The Role of Epigenetic Mechanisms
1.5.1 Chromatin Remodelling
1.5.2 Histone Variants
1.5.3 Histone Modification
1.5.3.1 Drivers of Dynamic Gene Regulation: Histone-Modifying Enzymes
1.5.4 DNA Methylation 1.6 Epigenetic Crosstalk --
Integrating Histone Modification and DNA Methylation1.7 Summary
References
Chapter 2 --
Enzyme and Protein Families that Regulate Histone Modifications and Crosstalk
2.1 Histones: Endless Variations on a Highly Conserved Theme
2.1.1 Organising DNA
2.1.2 Histone Genes
2.1.3 Post-Translational Modifications of Histones
2.2 How Histone Modifications Influence Chromatin Function
2.2.1 Associations between Modifications and Chromatin Function
2.2.2 Nucleosome Signalling and the Histone Code Hypothesis 2.3 Enzymes that Write Histone Modifications and Protein Domains that Read them2.3.1 Histone Acetylation
2.3.2 Histone Methylation
2.3.3 The Multiple Readers of Histone Methylation
2.3.4 Histone Phosphorylation
2.4 Interactions between Histone Modifications --
Crosstalk
2.4.1 Effects on Further Modification of the Same Histone Tail
2.4.2 Effects on Recognition of Nearby Modifications
2.4.3 Effects on Erasure of Nearby Modifications
2.5 The Importance of Protein Complexes
2.5.1 HDACs and their Inhibitors
2.6 Conclusions
Acknowledgements
References Chapter 3 --
Epigenetics and Disease3.1 Introduction
3.2 Congenital Mendelian Inherited Epigenetic Diseases
3.2.1 Mendelian Inherited Congenital Syndromes Involving Mutations in Genes that Encode DNA Methylation Readers and Modifiers
3.2.1.1 Mutations in the DNMT Genes
3.2.1.2 Mutations within DNA Methylation Readers
3.3 Mendelian Inherited Congenital Syndromes Involving Mutations in Genes that Encode Histone Modifiers
3.4 Mutations in Genes Encoding Nucleosomal Remodelling and Architectural Proteins
3.5 Congenital NMEDs Exemplified by Syndromes Due to Loss of Genomic Imprinting 3.6 Complex Disease and Epigenetics3.7 Conclusions
References
Chapter 4 --
Targeting DNA Methylation
4.1 Introduction
4.2 DNA Methylation and Its Role in Gene Expression
4.3 Reversal and Modification of DNA Methylation
4.4 Aberrant DNA Methylation in Cancer
4.5 DNA Methylation in Other Diseases
4.6 Structure and Mechanism of DNMTs
4.7 DNMT Inhibitors
4.7.1 Nucleoside DNMT Inhibitors
4.7.2 Non-Nucleoside DNMT Inhibitors
4.8 Outlook
Acknowledgements
References
Chapter 5 --
Targeting Histone Acetylation
5.1 Introduction
5.2 HDAC Proteins
5.2.1 Function of Histone Deacetylases

✦ Subjects

Epigenetics Drug development SCIENCE Life Sciences Biochemistry