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Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy
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 gliobl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143896/ https://www.ncbi.nlm.nih.gov/pubmed/21884623 http://dx.doi.org/10.1186/2043-9113-1-5 |
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author | Chandra, Nagasuma Bhagavat, Raghu Sharma, Eshita Sreekanthreddy, P Somasundaram, Kumaravel |
author_facet | Chandra, Nagasuma Bhagavat, Raghu Sharma, Eshita Sreekanthreddy, P Somasundaram, Kumaravel |
author_sort | Chandra, Nagasuma |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3143896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31438962011-07-27 Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy Chandra, Nagasuma Bhagavat, Raghu Sharma, Eshita Sreekanthreddy, P Somasundaram, Kumaravel J Clin Bioinforma Research 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. BioMed Central 2011-01-20 /pmc/articles/PMC3143896/ /pubmed/21884623 http://dx.doi.org/10.1186/2043-9113-1-5 Text en Copyright ©2011 Chandra et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Chandra, Nagasuma Bhagavat, Raghu Sharma, Eshita Sreekanthreddy, P Somasundaram, Kumaravel Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy |
title | Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy |
title_full | Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy |
title_fullStr | Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy |
title_full_unstemmed | Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy |
title_short | Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy |
title_sort | virtual screening, identification and experimental testing of novel inhibitors of pbef1/visfatin/nmprtase for glioma therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143896/ https://www.ncbi.nlm.nih.gov/pubmed/21884623 http://dx.doi.org/10.1186/2043-9113-1-5 |
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