2009
DOI: 10.1007/978-1-60761-274-2_13
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Hypothesis-Driven Screening

Abstract: Phenotypic chemogenomics studies require screening strategies that account for the complex nature of the experimental system. Unknown mechanism of action and high frequency of false positives and false negatives necessitate iterative experiments based on hypotheses formed on the basis of results from the previous step. Process-driven High Throughput Screening (HTS), aiming to "industrialize" lead finding and developed to maximize throughput, is rarely affording sufficient flexibility to design hypothesis-based… Show more

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Cited by 3 publications
(4 citation statements)
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“…Thiomuracin A (Th1, Table 18), identified from high throughput antibacterial screening against difficult-to-treat human pathogen S. aureus, was isolated from an extract of Nonomuraea strain Bp3714-39 [114]. Having the similar trisubstituted pyridine ring system as GE2270A, Th1 was found to target the elongation factor Tu (EF-Tu) of bacteria.…”
Section: Thiomuracin Amentioning
confidence: 99%
“…Thiomuracin A (Th1, Table 18), identified from high throughput antibacterial screening against difficult-to-treat human pathogen S. aureus, was isolated from an extract of Nonomuraea strain Bp3714-39 [114]. Having the similar trisubstituted pyridine ring system as GE2270A, Th1 was found to target the elongation factor Tu (EF-Tu) of bacteria.…”
Section: Thiomuracin Amentioning
confidence: 99%
“…We have recently reported a highthroughput cherry-picking system that allows rapid, iterative follow-up of large hit lists. 21 the primary hits were thus profiled in four concentrations under two different iPtG conditions (5 µM and 1 mM). the ratio of ic 50 under both iPtG conditions values was used to select compounds with apparent selectivity for the Mvas enzyme.…”
Section: Mvas Screenmentioning
confidence: 99%
“…the desire to run multiple rounds of cherry-picking in a short turnaround time, with concentrations and plate formats tailored to the experiment, put a large burden on compound logistics support. the flexibility offered by low-volume acoustic dispensing, implemented in a high-throughput cherry-picking system, 21 allowed us to repeatedly array >20 000 compounds in replicates and multiple concentrations in a matter of days. extensive profiling of hits could therefore be conducted.…”
Section: Mevalonate Rescuementioning
confidence: 99%
“…To address the need for novel chemical classes with new mechanisms of action and no cross-resistance with existing drugs, we screened a library of synthetic compounds, pure natural products and microbial extracts for antibacterial activity against the methicillin-and glycopeptide-resistant S. aureus strain Mu50 (11,15,23). The thiopeptide GE2270 A, a known inhibitor of bacterial elongation factor Tu (1,16), was identified as an antibacterial hit (Ͼ50% growth inhibition at 4 M) in the assay (20).…”
mentioning
confidence: 99%