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not. It has also been shown the specific analogs of diarylpentanoids have specific activities and
that only a minor change
in their composition modifies, or even abrogates, that activity.
Preliminary qRT-PCR (RNA analysis) and western blotting (protein analysis)
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found that
curcumin (while at lower micromolar concentrations) did not affect the expression of the androgen
level in prostate cancer cells whereas ca27 did show decreased expression of the androgen level
and other analogs of ca27 showed varied outcomes, indicating that there are some interactions
occurring and not simply interfering with the assay signaling. Other SAR studies have shown that
specific diarylpentanoids induce ROS and specific protein degradation
depending on their
structure. Finally, cheminformatic analysis of ca27 demonstrates more favorable parameters with
respect to the number of hydrogen bond donors/acceptors, logP, etc.
This information taken in
total highlight the probability that ca27 and its analogs are not PAINS molecules and are not simply
directly interfering with the assay signaling. In order to further ensure that PAINS are not a part
of this study, we are also operating under the assumption that there is direct binding between the
compounds and the AR, which would avoid the dilemma of determining whether the compound is
binding to the receptor or interfering with the assay.
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