AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications

Research output: Contribution to journal › Letter › Research › peer-review

Standard

AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications. / 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.

In: ACS Medicinal Chemistry Letters, 2024.

Research output: Contribution to journal › Letter › Research › peer-review

Harvard

Pippione, AC, Vigato, C, Tucciarello, C, Hussain, S, Salladini, E, Truong, HH, Henriksen, NM, Vanzetti, G, Giordano, G, Zonari, D, Mirza, OA, Frydenvang, K, Pignochino, Y, Oliaro-Bosso, S, Boschi, D & Lolli, ML 2024, 'AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications', ACS Medicinal Chemistry Letters. https://doi.org/10.1021/acsmedchemlett.4c00150

APA

Pippione, A. C., Vigato, C., Tucciarello, C., Hussain, S., Salladini, E., Truong, H. H., Henriksen, N. M., Vanzetti, G., Giordano, G., Zonari, D., Mirza, O. A., Frydenvang, K., Pignochino, Y., Oliaro-Bosso, S., Boschi, D., & Lolli, M. L. (Accepted/In press). AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications. ACS Medicinal Chemistry Letters. https://doi.org/10.1021/acsmedchemlett.4c00150

Vancouver

Pippione AC, Vigato C, Tucciarello C, Hussain S, Salladini E, Truong HH et al. AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications. ACS Medicinal Chemistry Letters. 2024. https://doi.org/10.1021/acsmedchemlett.4c00150

Author

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. / AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications. In: ACS Medicinal Chemistry Letters. 2024.

Bibtex

@article{797a7c367571461ab80588e78b99cd49,
title = "AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications",
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.",
keywords = "AI drug design, AKR1C3 inhibitors, doxorubicin., Osteosarcoma, Prostate Cancer",
author = "Pippione, {Agnese C.} and Chiara Vigato and Cristina Tucciarello and Samrina Hussain and Edoardo Salladini and Truong, {Ha H.} and Henriksen, {Niel M.} and Gaia Vanzetti and Giorgia Giordano and Daniele Zonari and Mirza, {Osman Asghar} and Karla Frydenvang and Ymera Pignochino and Simonetta Oliaro-Bosso and Donatella Boschi and Lolli, {Marco L.}",
note = "Publisher Copyright: {\textcopyright} 2024 American Chemical Society",
year = "2024",
doi = "10.1021/acsmedchemlett.4c00150",
language = "English",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications

AU - Pippione, Agnese C.

AU - Vigato, Chiara

AU - Tucciarello, Cristina

AU - Hussain, Samrina

AU - Salladini, Edoardo

AU - Truong, Ha H.

AU - Henriksen, Niel M.

AU - Vanzetti, Gaia

AU - Giordano, Giorgia

AU - Zonari, Daniele

AU - Mirza, Osman Asghar

AU - Frydenvang, Karla

AU - Pignochino, Ymera

AU - Oliaro-Bosso, Simonetta

AU - Boschi, Donatella

AU - Lolli, Marco L.

N1 - Publisher Copyright: © 2024 American Chemical Society

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - AI drug design

KW - AKR1C3 inhibitors

KW - doxorubicin.

KW - Osteosarcoma

KW - Prostate Cancer

U2 - 10.1021/acsmedchemlett.4c00150

DO - 10.1021/acsmedchemlett.4c00150

M3 - Letter

AN - SCOPUS:85197561581

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

ER -

ID: 398427450