Computer-guided discovery and optimization of inhibitors of DNA methyltransferases

Pause-conférences du CERMO-FC

 

Le CERMO-FC et le Pr Alexandre Gagnon ont le plaisir de vous inviter le Jeudi 6 juin à la présentation du

Pr José L. Medina-Franco,du département de pharmacie à la Universidad Nacional Autónoma de México (UNAM).

 

"Computer-Guided Discovery and Optimization of Inhibitors of DNA Methyltransferases"

Epigenetics is defined as the study of the chromosomal mechanisms that induce heritable changes in gene expression without modification of the DNA sequence and that lead to a stable phenotype. These epigenetic regulations can be mediated by the methylation of DNA or by post-translational modifications of the histones and affect the structure of the chromatin. DNA methylation is a stable epigenetic modification that leads to the methylation of cytosine and which plays an essential role in physiological processes. DNA methylation is catalyzed by DNA methyltransferases. The discovery of potent and selective inhibitors of DNMTs is of utmost importance for the development of novel therapies for the treatment of cancer and for the generation of tool compounds for studying the involvement of DNMTs in the development of various diseases. 5-Azacytidine (Vidaza) and 5-aza-2'-deoxycytidine (Dacogen) are DNMT inhibitors that have been approved by the FDA for the treatment of myelodysplastic syndrome and acute myeloid leukemia, respectively. Vidaza and Dacogen suffer from limitations that are a direct consequence of their nucleosidic structure such as poor pharmacokinetic profiles, low selectivity, and high toxicity. Consequently, there is an urgent need for new potent and selective non-nucleoside DNMT inhibitors that possess good pharmacokinetic profiles and that show minimal toxicity.In this seminar will discuss the identification of inhibitors of DNMTs by means of virtual screening of chemical databases followed by lead optimization efforts. We will also present the role of computational approaches to 1) explore the epigenetic relevant chemical space; 2) identify novel DNMT inhibitors from natural sources, and 3) guide the optimization of active compounds through molecular docking simulations of small molecules with crystal structures of DNMTs. 

 

Au plaisir de vous y voir en grand nombre.

 

Hermance BEAUD,

Coordinatrice du CERMO-FC

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jeudi 6 juin 2019
12 h à 13 h

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UQAM - Pavillon Président-Kennedy (PK)
PK-1140
201, avenue du Président-Kennedy
Montréal (QC)

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