Título del libro: Epi-Informatics: Discovery And Development Of Small Molecule Epigenetic Drugs And Probes
Título del capítulo: Computational Structure-Activity Relationship Studies of Epigenetic Target Inhibitors
OSCAR MENDEZ LUCIO;
Autores externos:
Idioma:
Inglés
Año de publicación:
2016
Palabras clave:
Activity cliffs; Activity landscape; Bromodomains; DNA methyltransferases; Epigenetics; Histone deacetylases; Pharmacophore; Proteochemometric modeling; QSAR; Structure-activity relationship
Resumen:
Epigenetics is an important driver of gene expression and hence it has a direct effect on the phenotype. For this reason, many of the proteins involved in epigenetic processes have been identified as attractive drug targets. Although some small molecules have been already approved by the US Food and Drug Administration as epigenetic modulators, many of them present several side effects. For this reason the search of new epigenetic modulators continues focusing on novel, selective, and safer compounds. In this regard, computational methods stand as useful tools to accelerate the discovery of new inhibitors. In this chapter we describe some of the most common computational methods used to gather structure-activity information of epi-drugs. Special emphasis is placed on ligand-based techniques such as pharmacophore, QSAR, and proteochemometric modeling. In addition, representative examples of how computational methods have helped the design of new inhibitors are discussed. Although numerous epigenetic targets have been described, this chapter will focus on DNA methyltransferases, histone deacetylases, and bromodomain inhibitors. Multitarget models are also discussed as a method to gain intrafamily selectivity. © 2016 Elsevier Inc. All rights reserved.
Entidades citadas de la UNAM:
ISBN:
9780128028094
Editorial:
Elsevier Inc. Nombre de la publicación:
Computational Structure-Activity Relationship Studies of Epigenetic Target Inhibitors
Página inicial:
359
Página final:
384
