title: Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy.
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.
authors: Bioinformatics Centre, Indian Institute of Science, Bangalore 560012, India. nchandra@serc.iisc.ernet.in.
authors: Nagasuma
authors: N
authors: Chandra
authors: Raghu
authors: R
authors: Bhagavat
authors: Eshita
authors: E
authors: Sharma
authors: P
authors: P
authors: Sreekanthreddy
authors: Kumaravel
authors: K
authors: Somasundaram