Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Selective inhibitors of aldo-keto reductases AKR1C1 and AKR1C3 discovered by virtual screening of a fragment library.

Authors: Brožič, Petra; Turk, Samo; Adeniji, Adegoke O; Konc, Janez; Janežič, Dušanka; Penning, Trevor M; Lanišnik Rižner, Tea; Gobec, Stanislav

Published In J Med Chem, (2012 Sep 13)

Abstract: Human aldo-keto reductases 1C1-1C4 (AKR1C1-AKR1C4) function in vivo as 3-keto-, 17-keto-, and 20-ketosteroid reductases and regulate the activity of androgens, estrogens, and progesterone and the occupancy and transactivation of their corresponding receptors. Aberrant expression and action of AKR1C enzymes can lead to different pathophysiological conditions. AKR1C enzymes thus represent important targets for development of new drugs. We performed a virtual high-throughput screen of a fragment library that was followed by biochemical evaluation on AKR1C1-AKR1C4 enzymes. Twenty-four structurally diverse compounds were discovered with low μM K(i) values for AKR1C1, AKR1C3, or both. Two structural series included the salicylates and the N-phenylanthranilic acids, and additionally a series of inhibitors with completely novel scaffolds was discovered. Two of the best selective AKR1C3 inhibitors had K(i) values of 0.1 and 2.7 μM, exceeding expected activity for fragments. The compounds identified represent an excellent starting point for further hit-to-lead development.

PubMed ID: 22881866 Exiting the NIEHS site

MeSH Terms: 20-Hydroxysteroid Dehydrogenases/antagonists & inhibitors*; 20-Hydroxysteroid Dehydrogenases/chemistry; 3-Hydroxysteroid Dehydrogenases/antagonists & inhibitors*; 3-Hydroxysteroid Dehydrogenases/chemistry; Aldo-Keto Reductase Family 1 Member C3; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors*; Hydroxyprostaglandin Dehydrogenases/chemistry; Molecular Docking Simulation; Molecular Dynamics Simulation; Salicylic Acid/chemistry

Back
to Top