Density Functional Theory QSAR Model for CDK6 Breast Cancer Inhibitors
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Authors
Gottschalk, Grace
Issue Date
2025-04-03
Type
Language
Keywords
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Abstract
Description
Breast cancer continues to affect millions of people worldwide, and the hormone receptor
+/human epidermal growth factor receptor 2- (HR+/HER2-) subtype is the most common.
Work in recent years to develop selective cyclin-dependent kinase (CDK) 6 inhibitors has
yielded promising results as a breast cancer therapy, but there is still an ongoing need to
develop drug candidates that are safe and effective. This study, which builds on the
experimental work of Chen et al. [J. Med. Chem. 2022, 65,15102-15122], aims to develop a
density functional theory (DFT) quantitative structure-activity relationship (QSAR) model
which can predict the effectiveness of CDK6 inhibitors based on single-molecule
properties. Q-Chem computational chemistry software was used to perform electronic
structure calculations and geometry optimizations for 29 drug candidates and several
isolated side chain and linker groups at the ωB97X-D/6-31G level of theory. The results of
these calculations provide physical and chemical information about these compounds
which can be correlated to their effectiveness as CDK6 inhibitors. Preliminary results
suggest that the polarity and van der Waals surface area of side chains and linker groups
are strongly correlated with drug activity, and work is currently being done to optimize the
fit and propose new drug candidates based on this QSAR model.