Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs has fallen much behind expectations during the past decade. Multi-target drugs multiply the number of pharmacologically relevant target molecules by introducing a set of indirect, network-dependent effects. Parallel with this, the ...

Modulation of protein-protein interactions (PPIs) with small molecules has been hampered by a lack of lucid methods capable of reliably identifying high-quality hits. In fragment screening, the low ligand efficiencies associated with PPI target sites pose significant challenges to fragment binding detection. Here, we investigate the requirements for ligand-based NMR techniques to detect rule-of...

The similarity property principle states that similar compounds have similar properties. In this study, we demonstrate that validity this principle holds well when the drug targets are protein domains. We leverage the similarity property principle to explore the druggability of CATH-FunFams, a type of protein domain and we use the associations between drugs and CATH-FunFams to explore drug poly...

Cytochrome c (cyt c) release from mitochondria is accepted to be the point of no return for eliciting a cascade of interactions that lead to apoptosis. A strategy for containing sustained apoptosis is to reduce the mitochondrial permeability pore opening. Pore opening is enhanced by peroxidase activity of cyt c gained upon its complexation with cardiolipin in the presence of reactive oxygen spe...

SUMO activating enzyme 1 (SUMO E1) is the first enzyme in sumoylation pathway and an important cancer drug target. However, only a few inhibitors were reported up to now that includes three natural products, semi-synthetic protein inhibitors and one AMP mimic. Here, we report the identification of quinazolinyloxy biaryl urea as a new class of SUMO E1 inhibitors. The most active compound of this...

The amount of solved protein structures is continuously growing. Pharmaceutical research recently recognized the potential of computationally extracting information from this large data pool and using them for homology-based knowledge transfer to new structures. This article focuses on computational approaches for structure-based target assessment. Highlighted are novel approaches for target cl...

SARS-CoV-2 contains a positive single-stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 elements were identified as conserved between SARS-CoV and SARS-CoV-2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these fold independently, in line with data from vivo ex-vivo structural probing experiments. These contain non-base-paired regi...

Control of parasite transmission is critical for the eradication of malaria. However, most antimalarial drugs are not active against P. falciparum gametocytes, responsible for the spread of malaria. Consequently, patients can remain infectious for weeks after the clearance of asexual parasites and clinical symptoms. Here we report the identification of 27 potent gametocytocidal compounds (IC50 ...

Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised poten...

Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brie...