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An Old NSAID Revisited: Crystal Structure of Aldose Reductase in Complex with Sulindac at 1.0 Å Supports a Novel Mechanism for its Anticancer and Antiproliferative Effects
Author(s) -
Steuber Holger
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100374
Subject(s) - sulindac , aldose reductase , mechanism of action , mechanism (biology) , chemistry , nonsteroidal , aldose reductase inhibitor , drug , anticancer drug , pharmacology , aldehyde reductase , enzyme , stereochemistry , biochemistry , medicine , in vitro , philosophy , epistemology
An old dog with new tricks! While sulindac, a nonsteroidal anti‐inflammatory drug (NSAID), has been extensively investigated as an anticancer agent, its mechanism of action remains poorly understood. The crystal structure of aldose reductase (ALR) in complex with sulindac rationalizes its inhibition of this enzyme—formerly considered an antidiabetic target—as a key mechanism for antitumor activity and supports further evaluation of ALR inhibitors as anticancer and antiproliferative drugs.