Title:Transcriptional Regulation of mPGES1 in Cancer: An Alternative Approach to Drug Discovery?
Volume: 18
Issue: 1
Author(s): Meera Ramanan, Mukesh Doble
Affiliation:
关键词:
癌症，炎症，抑制剂，前列腺素E合成酶 ，转录因子
摘要: 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.
