ChemProt: a disease chemical biology database

Abstract

Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical–protein annotation resources, as well as disease-associated protein–protein interactions (PPIs). We assembled more than 700 000 unique chemicals with biological annotation for 30 578 proteins. We gathered over 2-million chemical–protein interactions, which were integrated in a quality scored human PPI network of 428 429 interactions. The PPI network layer allows for studying disease and tissue specificity through each protein complex. ChemProt can assist in the in silico evaluation of environmental chemicals, natural products and approved drugs, as well as the selection of new compounds based on their activity profile against most known biological targets, including those related to adverse drug events. Results from the disease chemical biology database associate citalopram, an antidepressant, with osteogenesis imperfect and leukemia and bisphenol A, an endocrine disruptor, with certain types of cancer, respectively. The server can be accessed at http://www.cbs.dtu.dk/services/ChemProt/.

Novel Bayesian classification models for predicting compounds blocking hERG potassium channels

“…It has been reported that D 3 receptor antagonists tend to exhibit hERG toxicity [53] . The top 11-20 of the good features are from sertindole analogues, Wombat-PK database molecules and h5-HT 2A receptor antagonists, which are mostly strong hERG blockers [48,54,55] . The good features can be used as structural alerts for hERG toxicity.…”

Back to the Roots: Prediction of Biologically Active Natural Products from Ayurveda Traditional Medicine

“…[20] ChemProt is a repository of 700,000 unique chemicals with biological activity for more than 30,500 proteins, assembled from both proprietary and freely available databases, including ChEMBL (version chembl 05), [21] BindingDB, [22] PDSP Ki Database, [23] DrugBank (version 2.5), [24] PharmGKB, [25] WOMBAT (version 2009), WOMBAT-PK (version 2008), [26] PubChem bioassay (2010), [27] CTD (version 2009) [28] and STITCH (version STITCH 2.0). [29] The data set of small molecule drugs was downloaded from the DrugBank v. 2.5 [24] and consisted of 4887 compounds, referred to in DrugBank as "small molecule structures".…”

Mapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads

“…Since the anti-malarial properties of the 13 533 GSK compounds are based on an in vivo screen, we initially ventured a concerted systems chemical biology approach to create an interaction map of the active compounds from GSK on the parasite's protein space. ChemProt, 18 a database compiled in-house from multiple chemical-protein annotation resources, with more than 700 000 unique chemicals and biological annotation for 30 578 targets, was surveyed in two ways: firstly, for direct experimental bioactivity information concerning the 13 533 GSK compounds, and secondly, for predicted bioactivities via structural similarities with compounds from ChemProt, on the premise that structurally similar molecules are expected to exhibit similar biological activities.…”