Although it is certainly possible that they act through separate and distinct pathways, the ability of these structurally and functionally distinct compounds to inhibit the growth of cancer cells and their additive effects with tamoxifen raise the possibility that they might also act through a common molecular target.
A search through the ChEMBL database (https://www.ebi.ac.uk/chembl), containing 1,359,508 distinct compounds as of April 10 , 2014 revealed very few hits (<1%), mainly stereoisomers of the natural nucleosides in both furanosyl and pyranosyl configurations (Table 2).
In addition to the analysis of the pairs consisting of distinct compounds, we further performed the analysis of 53,800 pairs of replicates, where the same compound was tested under the same condition (i.e., cell line, dose, and treatment duration).
Thus, there is no evidence that the coelution of distinct compounds affects the validity of the GOF test.
p53-deficient (TP53−/−) human colon carcinoma HCT 116 cells or their p53-proficient wild-type (WT) counterparts stably expressing red fluorescent protein (RFP)- or green fluorescent protein (GFP -tagged histone 2B, respectively, were co-cultured in 96-well plates for 48 h in the absence or presence of 480 distinct compounds from the ICCB library of bioactive aGFP -tagged
The last column indicates the percentage of the total number of distinct compounds (3,228) annotated on each target.
In contemporary mineralogy disputes, Berzelius frequently sided with René-Just Haüy, who based his crystallography on the existence of distinct compounds as interpreted through Lavoisier's chemistry, and against the school of Abraham Gottlob Werner, who relied on external characters such as colour, texture, and hardness to discriminate between species of minerals.
Another future task is the further differentiation and separation of distinct compounds that now reside in a 'mixed pot', e.g. the group of 'frequency-lowering β-blockers' (FORTA list, p. 11), which formally still contains sotalol but which is now considered mainly as a class III antiarrhythmic (D drug), or propranolol, which should not be used (with exceptions) for pharmacokinetic reasons.
The results obtained here indicate that the anti-proliferative potency of EcEE is similar to that observed for some of its individual constituents such as eupatoriopicrin, jaceosidin and hispidulin, albeit without marked induction of DNA damage and therefore suggesting a combined action of distinct compounds.
