Inhibitors of Aldo-Keto Reductases AKR1C1-AKR1C4

Author(s): P. Brozic, S. Turk, T. Lanisnik Rizner, S. Gobec

Journal Name: Current Medicinal Chemistry

Volume 18 , Issue 17 , 2011

Become EABM
Become Reviewer
Call for Editor


The AKR1C aldo-keto reductases (AKR1C1-AKR1C4) are enzymes that interconvert steroidal hormones between their active and inactive forms. In this manner, they can regulate the occupancy and trans-activation of the androgen, estrogen and progesterone receptors. The AKR1C isoforms also have important roles in the production and inactivation of neurosteroids and prostaglandins, and in the metabolism of xenobiotics. They thus represent important emerging drug targets for the development of agents for the treatment of hormone-dependent forms of cancer, like breast, prostate and endometrial cancers, and other diseases, like premenstrual syndrome, endometriosis, catamenial epilepsy and depressive disorders. We present here the physiological roles of these enzymes, along with their structural properties and an overview of the recent developments regarding their inhibitors. The most important strategies of inhibitor design are described, which include the screening of banks of natural compounds (like cinnamic acids, flavonoids, jasmonates, and related compounds), the screening of and structural modifications to non-steroidal anti-inflammatory drugs, the substrate-inspired design of steroidal and nonsteroidal inhibitors, and computer-assisted structure-based inhibitor design.

Keywords: Aldo-keto reductases, cancer, drug discovery, enzyme inhibitors, flavonoids, non-steroidal anti-inflammatory drugs, steroids, synergistic, steroidal hormones, prostaglandins

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2011
Page: [2554 - 2565]
Pages: 12
DOI: 10.2174/092986711795933713
Price: $65

Article Metrics

PDF: 37