JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
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Transcriptional Regulation of mPGES1 in Cancer: An Alternative Approach to Drug Discovery?

Prostaglandins serve as the connecting link between inflammation and cancer. mPGES1, the downstream enzyme in the prostaglandin pathway is considered a better target than COX-2 against the progression of cancer due to the cardiovascular and other complications associated with the inhibition of the latter. Despite the discovery of several compounds that inhibit mPGES1 none could enter the market as drugs because of the problems concerning specificity and unacceptable pharmacokinetic properties. Expression of mPGES1 is inducible in conditions of inflammation and hypoxia and its expression is regulated by a number of transcriptional factors. Targeting these transcription factors could be an alternative approach in the drug discovery process. In this review, the characteristics of the transcription factors, their ability to bind to the promoter of mPGES1 gene and the inhibitors against them have been discussed. The Structure Activity Relationship of the reported inhibitors is highlighted. Finally, practical challenges to further the drug development and future research directions are discussed. These novel compounds that are inhibitors of the major transcription factors are promising candidates for further development as inhibitors of mPGES1.

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