Thiazolidinedione-Based PI3Kα Inhibitors: An Analysis of Biochemical and Virtual Screening Methods
Author Information
Author(s): Jo-Anne Pinson, Oleg Schmidt-Kittler, Jiuxiang Zhu, Ian G Jennings, Kenneth W Kinzler, Bert Vogelstein, David K Chalmers, Philip E Thompson
Primary Institution: Monash Institute of Pharmaceutical Sciences
Hypothesis
Can virtual screening methods effectively identify potent inhibitors of PI3Kα?
Conclusion
The study found that using higher resolution and ligand-bound structures for virtual screening significantly improved the identification of active compounds.
Supporting Evidence
- Seventy-three derivatives were screened as inhibitors of recombinant PI3Kα and PI3Kγ.
- Twelve compounds were found to have a sub-micromolar IC50 value against PI3Kα.
- Docking results were improved by using higher resolution structures and liganded structures of the PI3Kγ and PI3Kδ isoforms.
Takeaway
The researchers tested a lot of compounds to find out which ones could stop a specific enzyme related to cancer, and they found some that worked really well.
Methodology
The study involved synthesizing and screening 73 thiazolidinedione derivatives against PI3Kα and PI3Kγ using in vitro assays and virtual screening methods.
Potential Biases
Potential off-target effects due to the broad activity of thiazolidinedione derivatives.
Limitations
The study's findings may not fully translate to in vivo effectiveness, and the docking models may not predict relative potencies accurately.
Digital Object Identifier (DOI)
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