2018
DOI: 10.1080/14756366.2018.1540474
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Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening

Abstract: Inosine 5′-monophosphate dehydrogenase (IMPDH) is an essential enzyme for the production of guanine nucleotides. Disruption of IMPDH activity has been explored as a therapeutic strategy for numerous purposes, such as for anticancer, immunosuppression, antiviral, and antimicrobial therapy. In the present study, we established a luciferase-based high-throughput screening system to identify IMPDH inhibitors from our chemical library of known bioactive small molecules. The screening of 1400 compounds resulted in t… Show more

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Cited by 19 publications
(16 citation statements)
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“…Ebselen has been found to have therapeutic potential against many infectious diseases. In most cases, ebselen acts as a covalent inhibitor of numerous thiol-dependent enzymes or functional proteins in various pathogens [ 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ]. The selenol derived from ebselen is reactive to cysteine residues in proteins.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Ebselen has been found to have therapeutic potential against many infectious diseases. In most cases, ebselen acts as a covalent inhibitor of numerous thiol-dependent enzymes or functional proteins in various pathogens [ 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ]. The selenol derived from ebselen is reactive to cysteine residues in proteins.…”
Section: Introductionmentioning
confidence: 99%
“…Following a high intake of dietary selenium or supranutritional selenium supplementation beyond the requirement for selenoprotein biosynthesis, small molecular weight selenium compounds are accumulated [ 140 , 141 , 142 , 143 , 144 , 145 ]. Hydrogen selenide, methylselenol, dimethylselenide and dimethyldiselenide are volatile small molecules and thus are likely to be found in the respiratory tract [ 147 , 153 , 154 ].…”
Section: Introductionmentioning
confidence: 99%
“…If inhibited, the imbalance between the guanine and adenine nucleotide pools has dramatic consequences for cell proliferation 16 , rendering IMPDHs into a suitable cellular target of drugs widely used to date in chemotherapy as antivirals or as immunosuppressive and antitumor agents 17 . Due to the crucial role in de novo nucleotide biosynthesis and the significant clinical relevance, IMPDHs from various species are in the focus of investigations 18,19 .…”
mentioning
confidence: 99%
“…Mycophenolate mofetil is a prodrug of mycophenolic acid [60], yielding K i = 24.42 µM ( Figure S7e). Three compounds, namely, disulfiram, bronopol, and ebselen, have been repurposed as IMPDH inhibitors [61]. Bronopol had the best inhibitory effect with K i = 234 nM (Figure 5a).…”
Section: Inhibitory Assay Against Clas Impdh∆98-201 Enzyme Activitymentioning
confidence: 99%