Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment

Tomasz M. Wróbel; Flemming Steen Jørgensen; Amit V. Pandey; Angelika Grudzińska; Katyayani Sharma; Jibira Yakubu; Fredrik Björkling

doi:10.1021/acs.jmedchem.3c00442

Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment

Tomasz M. Wróbel^*, Flemming Steen Jørgensen, Amit V. Pandey, Angelika Grudzińska, Katyayani Sharma, Jibira Yakubu, Fredrik Björkling

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Review › Forskning › peer review

16 Citationer (Scopus)

15 Downloads (Pure)

Abstract

CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	66
Udgave nummer	10
Sider (fra-til)	6542–6566
ISSN	0022-2623
DOI	https://doi.org/10.1021/acs.jmedchem.3c00442
Status	Udgivet - 2023

Bibliografisk note

Funding Information:
T.M.W.’s work is funded by the Narodowe Centrum Nauki grant Sonata 16 2020/39/D/NZ7/00572. A.V.P. acknowledges the Swiss National Science Foundation, grant number 310030M_204518, and Cancer Research Switzerland, grant number KFS-5557-02-2022. J.Y. and K.S. are funded by Swiss Government Excellence Scholarships (ESKAS), grant numbers 2022.0470 and 2019.0385.

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society

Adgang til dokumentet

10.1021/acs.jmedchem.3c00442

FulltextForlagets udgivne version, 11,1 MBLicens: CC BY

Citationsformater

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title = "Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment",

abstract = "CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.",

author = "Wr{\'o}bel, {Tomasz M.} and J{\o}rgensen, {Flemming Steen} and Pandey, {Amit V.} and Angelika Grudzi{\'n}ska and Katyayani Sharma and Jibira Yakubu and Fredrik Bj{\"o}rkling",

note = "Funding Information: T.M.W.{\textquoteright}s work is funded by the Narodowe Centrum Nauki grant Sonata 16 2020/39/D/NZ7/00572. A.V.P. acknowledges the Swiss National Science Foundation, grant number 310030M_204518, and Cancer Research Switzerland, grant number KFS-5557-02-2022. J.Y. and K.S. are funded by Swiss Government Excellence Scholarships (ESKAS), grant numbers 2022.0470 and 2019.0385. Publisher Copyright: {\textcopyright} 2023 The Authors. Published by American Chemical Society",

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language = "English",

volume = "66",

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TY - JOUR

T1 - Non-steroidal CYP17A1 Inhibitors

T2 - Discovery and Assessment

AU - Wróbel, Tomasz M.

AU - Jørgensen, Flemming Steen

AU - Pandey, Amit V.

AU - Grudzińska, Angelika

AU - Sharma, Katyayani

AU - Yakubu, Jibira

AU - Björkling, Fredrik

N1 - Funding Information: T.M.W.’s work is funded by the Narodowe Centrum Nauki grant Sonata 16 2020/39/D/NZ7/00572. A.V.P. acknowledges the Swiss National Science Foundation, grant number 310030M_204518, and Cancer Research Switzerland, grant number KFS-5557-02-2022. J.Y. and K.S. are funded by Swiss Government Excellence Scholarships (ESKAS), grant numbers 2022.0470 and 2019.0385. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society

PY - 2023

Y1 - 2023

N2 - CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.

AB - CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.

U2 - 10.1021/acs.jmedchem.3c00442

DO - 10.1021/acs.jmedchem.3c00442

M3 - Review

C2 - 37191389

AN - SCOPUS:85160203123

VL - 66

SP - 6542

EP - 6566

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 10

ER -