Fragment Screening Reveals Novel Scaffolds against Sirtuin-2-Related Protein 1 from .

Sirtuin-2 (Sir2) is a histone deacetylase recognized as an antitrypanosomal target, yet there is limited knowledge regarding their potent inhibitors. This investigation employs the fragment-based drug discovery (FBDD) framework to identify novel inhibitors against Sir2-related protein 1. Initially, frequent residue-ligand interactions extracted from the crystallographic structures of human Sir2 and key features of human and parasitic Sir2 active sites were utilized to curate a targeted fragment library.

SETDB1 as a cancer target: challenges and perspectives in drug design.

Genome stability is governed by chromatin structural dynamics, which modify DNA accessibility under the influence of intra- and inter-nucleosomal contacts, histone post-translational modifications (PTMs) and variations, besides the activity of ATP-dependent chromatin remodelers. These are the main ways by which chromatin dynamics are regulated and connected to nuclear processes, which when dysregulated can frequently be associated with most malignancies. Recently, functional crosstalk between histone modifications and chromatin remodeling has emerged as a critical regulatory method of transcriptional regulation during cell destiny choice.

Convergent QSAR Models for the Prediction of Cruzain Inhibitors.

Chagas disease is a parasitosis caused by . Cruzain, the major cysteine protease from , is an excellent therapeutic target in the search for antichagasic drugs. It is important in the role of cell invasion, replication, differentiation, and metabolism of the parasite.