AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications
Research output: Contribution to journal › Letter › Research › peer-review
AKR1C3 is an upregulated enzyme in prostate and other cancers; in addition to regulating hormone synthesis, this enzyme is thought to play a role in the aggressiveness of tumors and in the defense against drugs. We here used an unbiased method to discover new potent AKR1C3 inhibitors: through an AI-based virtual drug screen, compound 4 was identified as a potent and selective enzymatic inhibitor able to translate this activity into a pronounced antiproliferative effect in the 22RV1 prostate cancer cell model. As other known AKR1C3 inhibitors, compound 4 determined a significantly increased activity of abiraterone, a drug approved for advanced prostate cancer. Compound 4 also showed a synergic effect with doxorubicin in osteosarcoma cell lines; specifically, the effect is correlated with AKR1C3 expression. In this research work, therefore, the use of AI allowed the identification of a new structure as an AKR1C3 inhibitor and its potential to enhance the effect of chemotherapeutics.
Original language | English |
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Journal | ACS Medicinal Chemistry Letters |
Volume | 15 |
Issue number | 8 |
Pages (from-to) | 1269–1278 |
ISSN | 1948-5875 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© 2024 American Chemical Society
- AI drug design, AKR1C3 inhibitors, doxorubicin., Osteosarcoma, Prostate Cancer
Research areas
ID: 398427450