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The availability of interaction data between small molecule drugs and protein targets has increased substantially in recent years. Using seven different databases, we were able to assemble a total of 4767 unique interactions between 802 drugs and 480 targets, which means that on average every drug is currently acknowledged to interact with 6 targets. The(More)
The practical implementation and validation of a ligand-based approach to mining the chemogenomic space of drugs is presented and applied to the in silico target profiling of 767 drugs against 684 targets of therapeutic relevance. The results reveal that drugs targeting aminergic G protein-coupled receptors (GPCRs) show the most promiscuous pharmacological(More)
983 1.7. The topology of this drug-target network reveals a well-organized modular structure, with many proteins naturally clustering around phylogenetic families. The nLCC values for the corresponding drug and target networks are 0.60 and 0.42, respectively. Both these numbers are significantly smaller than the values of 0.90 and 0.78 obtained from(More)
The association between molecular size and risk of failure has promoted the use of binding efficiency as a prioritization metric in lead selection. Even though by extension it is often referred to as "ligand efficiency", the concept was originally conceived to be strictly applicable to comparing the binding efficiencies of ligands for a single target. With(More)
Bioactive ligands are a valuable and increasingly accessible source of information about protein targets. On the basis of this statement, a list of 25 nuclear receptors was described by a series of bioactive ligands extracted directly from bibliographical sources, stored properly in an annotated chemical library, and mathematically represented using the(More)
A novel set of molecular descriptors called SHED (SHannon Entropy Descriptors) is presented. They are derived from distributions of atom-centered feature pairs extracted directly from the topology of molecules. The value of a SHED is then obtained by applying the information-theoretical concept of Shannon entropy to quantify the variability in a(More)
One of the grand challenges in chemical biology is identifying a small-molecule modulator for each individual function of all human proteins. Instead of targeting one protein at a time, an efficient approach to address this challenge is to target entire protein families by taking advantage of the relatively high levels of chemical promiscuity observed(More)
The design of chemical libraries directed to target classes is an activity that requires the availability of ligand pharmacological data and/or protein structural data. On the basis of the knowledge derived from these data, chemical libraries directed mainly to G protein-coupled receptors, kinases, proteases, and nuclear receptors have been assembled.(More)
Molecular profiling efforts aim at characterizing the biological actions of small molecules by screening them in hundreds of different biochemical and/or cell-based assays. Together, these assays yield a rich data landscape of target-based and phenotypic effects of the tested compounds. However, submitting an entire compound library to a molecular profiling(More)
Aberrant activation of signaling pathways plays a pivotal role in central nervous system disorders, such as Alzheimer's disease (AD). Using a combination of virtual screening and experimental testing, novel small molecule inhibitors of tPA-mediated extracellular signal-regulated kinase (Erk)1/2 activation were identified that provide higher levels of(More)