Chandra, Nagasuma ; Bhagavat, Raghu ; Sharma, Eshita ; Sreekanthreddy, P. ; Somasundaram, Kumaravel (2011) Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy Journal of Clinical Bioinformatics, 1 . 5_1-5_12. ISSN 2043-9113
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Official URL: http://www.jclinbioinformatics.com/content/1/1/5
Related URL: http://dx.doi.org/10.1186/2043-9113-1-5
Abstract
Background: Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes nicotinamide phosphoribosyltransferase (NMPRTase), which catalyses the rate limiting step in the salvage pathway of NAD+ metabolism in mammalian cells. PBEF1 transcript and protein levels have been shown to be elevated in glioblastoma and a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer cells. Methods: Virtual screening using docking was used to screen a library of more than 13,000 chemical compounds. A shortlisted set of compounds were tested for their inhibition activity in vitro by an NMPRTase enzyme assay. Further, the ability of the compounds to inhibit glioma cell proliferation was carried out. Results: Virtual screening resulted in short listing of 34 possible ligands, of which six were tested experimentally, using the NMPRTase enzyme inhibition assay and further with the glioma cell viability assays. Of these, two compounds were found to be significantly efficacious in inhibiting the conversion of nicotinamide to NAD+, and out of which, one compound, 3-amino-2-benzyl-7-nitro-4-(2-quinolyl-)-1,2-dihydroisoquinolin-1-one, was found to inhibit the growth of a PBEF1 over expressing glioma derived cell line U87 as well. Conclusions: Thus, a novel inhibitor has been identified through a structure based drug discovery approach and is further supported by experimental evidence.
Item Type: | Article |
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Source: | Copyright of this article belongs to BioMed Central. |
ID Code: | 49682 |
Deposited On: | 20 Jul 2011 14:00 |
Last Modified: | 18 May 2016 04:17 |
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