Potential mechanistic explanations.
Although this correlation is of modest potency, it supports our mechanistic observations in vitro, as regulation of ERα expression in cells depends on a multiplicity of factors, with PRDX1-mediated protection representing only one.
The IARC decision seems unreasonable because peroxisome proliferation alone does not provide a mechanistic explanation for the different carcinogenic potencies of peroxisome proliferators in the rat liver (Marsman et al. 1988).
In addition, these studies lend support to the idea that different types of stem cells, as well as some cancer cells, share common features of chromatin structure that allow them to maintain their developmental potency, and provide one possible mechanistic link underlying this commonality.
The variety in anticancer activity and potency of these compounds suggests potential mechanistic diversity in this set of small molecules, in addition to the existing structural diversity.
We conclude that mechanistic understanding of differences in species sensitivity or toxic potency of chemicals is more likely to succeed if biotransformation kinetics are considered.
29 Notably, available mechanistic data comparing individual macrolides suggest that clarithromycin has higher potency of IKr inhibition compared with roxithromycin.
32 It is unknown at this time, however, whether these mechanistic differences can translate to improved safety, tolerability, efficacy, or potency over rituximab.
At a mechanistic level, adding an N-3 methyl-carbamoyl group significantly strengthens potency of the resulting compound because occupancy of the N-3 side pocket of the "M" site is structurally favorable to inhibit the GluA1.
Unfortunately, the hits emerging from high-throughput screens for cytotoxic agents were historically prioritized using factors such as potency, ease of synthesis, drug-like characteristics, structural and mechanistic novelty, and intellectual property considerations [ 1].
