PubChem as a public resource for drug discovery

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Drug discovery today (Impact Factor: 6.69). 10/2010; 15(23-24):1052-7. DOI: 10.1016/j.drudis.2010.10.003
Source: PubMed


PubChem is a public repository of small molecules and their biological properties. Currently, it contains more than 25 million unique chemical structures and 90 million bioactivity outcomes associated with several thousand macromolecular targets. To address the potential utility of this public resource for drug discovery, we systematically summarized the protein targets in PubChem by function, 3D structure and biological pathway. Moreover, we analyzed the potency, selectivity and promiscuity of the bioactive compounds identified for these biological targets, including the chemical probes generated by the NIH Molecular Libraries Program. As a public resource, PubChem lowers the barrier for researchers to advance the development of chemical tools for modulating biological processes and drug candidates for disease treatments.

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    • "Molecular docking analysis of the modeled protein structures was carried out to identify if substitutions in the amino acid sequences of blaA resulted in variations in their binding affinity to β-lactam antibiotic amoxicillin and the β-lactamase inhibitor clavulanic acid. The structures of amoxicillin and clavulanic acid were retrieved from the PubChem compound database ( Subsequently the downloaded SDF file was converted to PDB format using iBabel. "
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    ABSTRACT: Beta-lactams are used as major therapeutic agents against a number of infectious agents. Due to widespread use of β-lactams, β-lactamases have evolved at a rapid pace leading to treatment failures. Yersinia enterocolitica causes many gastrointestinal problems. It is an extremely heterogeneous species comprising more than fifty serotypes and six biotypes which differ in their ecological niches, geographical distribution and pathogenic potential. Though biotype 1A strains have been associated with outbreaks of Yersiniosis, there has been a controversy regarding their pathogenicity. The strains of Y. enterocolitica isolated from India belonged to biotype 1A and possessed genes for two β-lactamases namely, blaA and blaB. An earlier study by us reported differential expression of blaA by strains of Y. enterocolitica biotype 1A. The present study has been carried out to understand the molecular bases which regulate the expression of blaA in Y. enterocolitica biotype 1A. We concluded that six types of blaA variants were present in strains of biotype 1A. Neither amino acid substitutions in blaA nor mutations in promoter regions of blaA contributed to differential expression of blaA in Y. enterocolitica biotype 1A. Rather, the secondary structures attained by mRNA of blaA might underlie the differential expression of blaA in Y. enterocolitica.
    Scientific Reports 06/2014; 4:5270. DOI:10.1038/srep05270 · 5.58 Impact Factor
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    • "3-Dimensional (3D) structures of the PBPs were obtained from Protein Data Bank (PDB) (Berman et al. 2000). 3D structures of PBPs were visualized through Py- MOL viewer (Lill and Danielson 2010). Co-crystallized ligands were identified and removed from the target proteins then water molecules removed and H atoms were added to the structure and minimizations were performed using Swiss pdb viewer (Guex and Peitsch 1997). "
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    ABSTRACT: Upper respiratory tract infection (URTI) is an acute infection which involves the upper respiratory tract: nose, sinuses, tonsils and pharynx. URT infections are caused mainly by pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Conventionally, β-lactam antibiotics are used to treat URT infections. Penicillin binding proteins (PBPs) catalyze the cell wall synthesis in bacteria. β-Lactam antibiotics like Penicillin, Cephalosporins, Carbapenems and Monobactams inhibit bacterial cell wall synthesis by binding with PBPs. Pathogenic bacteria have efficiently evolved to resist these β-lactam antibiotics. New generation antibiotics are capable of inhibiting the action of PBP due to its new and peculiar structure. New generation antibiotics and Penicillin derivatives are selected in this study and virtually compared on the basis of interaction studies. 3-Dimensional (3D) interaction studies between Lactivicin, Cefuroxime, Cefadroxil, Ceftaroline, Ceftobiprole and Penicillin derivatives with PBPs of the above-mentioned bacteria are carried out. The aim of this study was to suggest a potent new generation molecule for further modification to increase the efficacy of the drug for the URTI.
    06/2014; 4(3). DOI:10.1007/s13205-013-0147-z
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    • "In order to gather all available information about ingredients of herbal medicines, we performed an extensive literature search for each herbal medicine. Structure files of molecules were downloaded from PubChem [18] Compound database, ChEMBL [19] and ChemSpider [20], or produced by ISIS Draw 2.5 (MDL Information Systems, Inc.) and further optimized by Sybyl 6.9 (Tripos, Inc.) with Sybyl force field and default parameters [2,21]. Different format types of the chemical files were converted to SDF format by Open Babel [22]. "
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    ABSTRACT: Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed.Description: The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski's rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development. The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at
    Journal of Cheminformatics 04/2014; 6(1):13. DOI:10.1186/1758-2946-6-13 · 4.55 Impact Factor
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