Data di Pubblicazione:
2024
Abstract:
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.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
AKR1C3 inhibitors, AI drug design, Prostate Cancer, Osteosarcoma, doxorubicin
Elenco autori:
Pippione, Agnese C.; Vigato, Chiara; Tucciarello, Cristina; Hussain, Samrina; Salladini, Edoardo; Truong, Ha H.; Henriksen, Niel M.; Vanzetti, Gaia; Giordano, Giorgia; Zonari, Daniele; Mirza, Osman Asghar; Frydenvang, Karla; Pignochino, Ymera; Oliaro-Bosso, Simonetta; Boschi, Donatella; Lolli, Marco L.
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