The structural basis of aldo-keto reductase 1C3 inhibition by 17α-picolyl and 17(E)-picolinylidene androstane derivatives
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00639306" target="_blank" >RIV/61388963:_____/25:00639306 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1080/14756366.2025.2551979" target="_blank" >https://doi.org/10.1080/14756366.2025.2551979</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/14756366.2025.2551979" target="_blank" >10.1080/14756366.2025.2551979</a>
Alternative languages
Result language
angličtina
Original language name
The structural basis of aldo-keto reductase 1C3 inhibition by 17α-picolyl and 17(E)-picolinylidene androstane derivatives
Original language description
Human aldo-keto reductase 1C3 (AKR1C3) is a steroid modifying enzyme involved in cancer progression. Here, A-ring modified 17 alpha-picolyl and 17(E)-picolinylidene androstane derivatives are shown to inhibit AKR1C3 activity in vitro. None of the androstane derivatives have off-target affinity for the androgen receptor, based on a fluorescence assay in yeast cells. The X-ray structure of AKR1C3 in complex with the strongest inhibitor, a 17 alpha-picolyl androstane with a C3-oxime modification, was determined at 1.7 & Aring, resolution. Based on this crystal structure and molecular docking, inhibition of AKR1C3 by the 17 alpha-picolyl or 17(E)-picolinylidene derivatives depends on interactions between the C3 modification and the NADP+ cofactor, while the C17 alpha-picolyl or C17-picolinylidene group anchors the inhibitor to AKR1C3. Because one AKR1C3 inhibitor identified here was also previously reported to inhibit CYP17, it may be possible for future researchers to design dual AKR1C3/CYP17 inhibitors based on a steroid scaffold for potential treatment of advanced prostate cancers.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Enzyme Inhibition and Medicinal Chemistry
ISSN
1475-6366
e-ISSN
1475-6374
Volume of the periodical
40
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
20
Pages from-to
2551979
UT code for WoS article
001564429000001
EID of the result in the Scopus database
2-s2.0-105015068341