Dienone Compounds: Targets and Pharmacological Responses.
Martina Bazzaro1, Stig Linder2,3
1Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Journal of Medicinal Chemistry
|November 4, 2020
Summary
Dienone compounds selectively target the ubiquitin-proteasome system (UPS), crucial for cancer cell survival. These compounds show promise against apoptosis-resistant tumors and in animal models.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Cancer Research
Background:
- Dienone compounds with a 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore exhibit significant tumor cell selectivity.
- Despite general thiol reactivity, these compounds demonstrate targeted biological responses.
Purpose of the Study:
- To review in vitro and preclinical studies of specific dienone compounds.
- To elucidate the mechanisms of action and therapeutic potential of dienone compounds.
Main Methods:
- Review of in vitro and preclinical studies.
- Analysis of gene expression profiling and cellular reporter protein experiments.
- Examination of reported mechanisms including UPS inhibition, p53 reactivation, and protein cross-linking.
Main Results:
- Dienone compounds (e.g., b-AP15, VLX1570, EF24) target the ubiquitin-proteasome system (UPS).
- UPS inhibition correlates with proteasome inhibition and subsequent cell death.
- Other mechanisms include p53 reactivation and protein cross-linking.
Conclusions:
- Dienone compounds are cytotoxic to apoptosis-resistant tumor cells.
- These compounds show efficacy in animal tumor models.
- While broadly reactive, dienones offer therapeutic potential against cancer.
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