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 -