Integrated Chemoinformatics
Approaches Toward Epigenetic
Drug Discovery
Saurabh Loharch, Vikrant Karmahapatra, Pawan Gupta,
Rethi Madathil and Raman Parkesh
Abstract Epigenetics has become an important field of research in drug discovery.
Epigenetic mechanisms are dynamic in nature and play a fundamental role in
cellular processes. Dysregulation of epigenetic events, including cross-talk between
DNA methylation and histone modifications, not only affects gene expression but
also causes pathophysiological effects leading to cancer, aging, cardiovascular,
neurological, and metabolic disorders. Epigenetic targets have captured the attention of researchers from diverse backgrounds to identify potential drugs for various
diseases. However, drug development is a complex, time-consuming process and
challenged by the high attrition rate. As with many chemotherapeutics, it is pertinent to avoid possible risk factors in epigenetic drug discovery. In this context,
computational approaches can rationally guide the search for active compounds by
utilizing the accumulated epigenetics knowledge base. In this chapter, we have
described the chemoinformatic strategies that can be applied to facilitate the
early-stage lead discovery in epigenetics, based on current best practices.
Keywords Chemoinformatics Á Epigenetics Á Drug discovery Á Screening library
Scaffolds Á Chemical space
Abbreviations
ATP
Adenosine triphosphate
CTCL Cutaneous T cell lymphoma
DNA
Deoxyribonucleic acid
DNMT DNA methyltransferase
FDA
Food and Drug Administration
HDAC Histone deacetylases
miRNA MicroRNA
RNA
Ribonucleic acid
S. Loharch Á V. Karmahapatra Á P. Gupta Á R. Madathil Á R. Parkesh (&)
Advanced Protein Science Building, Institute of Microbial Technology,
Chandigarh 160036, India
e-mail: rparkesh@imtech.res.in
© Springer Nature Switzerland AG 2019
C. G. Mohan (ed.), Structural Bioinformatics: Applications in Preclinical Drug
Discovery Process, Challenges and Advances in Computational Chemistry
and Physics 27, https://doi.org/10.1007/978-3-030-05282-9_8
247
Approaches Toward Epigenetic
Drug Discovery
Saurabh Loharch, Vikrant Karmahapatra, Pawan Gupta,
Rethi Madathil and Raman Parkesh
Abstract Epigenetics has become an important field of research in drug discovery.
Epigenetic mechanisms are dynamic in nature and play a fundamental role in
cellular processes. Dysregulation of epigenetic events, including cross-talk between
DNA methylation and histone modifications, not only affects gene expression but
also causes pathophysiological effects leading to cancer, aging, cardiovascular,
neurological, and metabolic disorders. Epigenetic targets have captured the attention of researchers from diverse backgrounds to identify potential drugs for various
diseases. However, drug development is a complex, time-consuming process and
challenged by the high attrition rate. As with many chemotherapeutics, it is pertinent to avoid possible risk factors in epigenetic drug discovery. In this context,
computational approaches can rationally guide the search for active compounds by
utilizing the accumulated epigenetics knowledge base. In this chapter, we have
described the chemoinformatic strategies that can be applied to facilitate the
early-stage lead discovery in epigenetics, based on current best practices.
Keywords Chemoinformatics Á Epigenetics Á Drug discovery Á Screening library
Scaffolds Á Chemical space
Abbreviations
ATP
Adenosine triphosphate
CTCL Cutaneous T cell lymphoma
DNA
Deoxyribonucleic acid
DNMT DNA methyltransferase
FDA
Food and Drug Administration
HDAC Histone deacetylases
miRNA MicroRNA
RNA
Ribonucleic acid
S. Loharch Á V. Karmahapatra Á P. Gupta Á R. Madathil Á R. Parkesh (&)
Advanced Protein Science Building, Institute of Microbial Technology,
Chandigarh 160036, India
e-mail: rparkesh@imtech.res.in
© Springer Nature Switzerland AG 2019
C. G. Mohan (ed.), Structural Bioinformatics: Applications in Preclinical Drug
Discovery Process, Challenges and Advances in Computational Chemistry
and Physics 27, https://doi.org/10.1007/978-3-030-05282-9_8
247