TY - JOUR
AU - Peter, Gedeck
AB - The biochemical half maximal inhibitory concentration (IC 50 ) is the most commonly used metric for on-target activity in lead optimization. It is used to guide lead optimization, build large-scale chemogenomics analysis, off-target activity and toxicity models based on public data. However, the use of public biochemical IC 50 data is problematic, because they are assay specific and comparable only under certain conditions. For large scale analysis it is not feasible to check each data entry manually and it is very tempting to mix all available IC 50 values from public database even if assay information is not reported. As previously reported for K i database analysis, we first analyzed the types of errors, the redundancy and the variability that can be found in ChEMBL IC 50 database. For assessing the variability of IC 50 data independently measured in two different labs at least ten IC 50 data for identical protein-ligand systems against the same target were searched in ChEMBL. As a not sufficient number of cases of this type are available, the variability of IC 50 data was assessed by comparing all pairs of independent IC 50 measurements on identical protein-ligand systems. The standard deviation of IC 50 data is only 25% larger than the standard deviation of K i data, suggesting that mixing IC 50 data from different assays, even not knowing assay conditions details, only adds a moderate amount of noise to the overall data. The standard deviation of public ChEMBL IC 50 data, as expected, resulted greater than the standard deviation of in-house intra-laboratory/inter-day IC 50 data. Augmenting mixed public IC 50 data by public K i data does not deteriorate the quality of the mixed IC 50 data, if the K i is corrected by an offset. For a broad dataset such as ChEMBL database a K i - IC 50 conversion factor of 2 was found to be the most reasonable.
TI - Comparability of Mixed IC 50 Data – A Statistical Analysis
JF - PLoS ONE
DO - 10.1371/journal.pone.0061007
DA - 2013-04-16
UR - https://www.deepdyve.com/lp/public-library-of-science-plos-journal/comparability-of-mixed-ic-50-data-a-statistical-analysis-J1e03eSng3
VL - 8
IS - 4
DP - DeepDyve
ER -