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In an effort to design an assay paradigm for the development of JAK2 selective inhibitors, we investigated whether compound selectivity differed between cellular and purified enzyme environments.
To each target the ChEMBL database associates a confidence score (see the Compound Selectivity example).
Using compound selectivity engineering and CRISPR/Cas9 genome editing, we reveal distinct functions for Erk5 and Brd4 in pluripotency regulation.
Compound selectivity against GSK-3β was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.
In order to return the largest possible dataset, the confidence score has been ignored in this example compound selectivity use case.
Known substrates and inhibitors of these transporters are showing a great structural variety, however, there exists some overlap in compound selectivity between the two.
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Very high azoxy-compound selectivity was achieved under green mild conditions.
These fragments turned out to determine compounds' selectivity between AChE and BuChE.
Although α2-adrenoceptor affinity decreased for these compounds, selectivity was not gained over the parent 3-hydroxymethyl compounds (1, 2) due to a loss in PNMT inhibitory potency.
For these active compounds, selectivity with respect to the closely-related aldehyde reductase was determined by measuring the corresponding inhibitory activities.
Docking experiments on HD1-A and HD1-B homology models revealed that the different compounds selectivity profiles could be addressed to different binding modes as observed for the reference compound SAHA.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com