AI Article Synopsis
- Researchers have created a new series of selective inhibitors for a specific enzyme called mPGES-1, based on a compound known as MK-886.
- The most effective compounds, identified as 23 and 30, demonstrate strong inhibition of mPGES-1 at very low concentrations and show at least 100 times more selectivity compared to other similar enzymes and compounds.
- These inhibitors successfully reduce PGE2 production in cell tests, although their effectiveness and selectivity are lower in these biological assays compared to the isolated enzyme tests.
Article Abstract
A series of potent and selective inhibitors of the inducible microsomal PGE2 synthase (mPGES-1) has been developed based on the indole FLAP inhibitor MK-886. Compounds 23 and 30 inhibit mPGES-1 with potencies in the low nanomolar range and with selectivities of at least 100-fold compared to their inhibition of mPGES-2, thromboxane synthase and binding affinity to FLAP. They also block the production of PGE2 in cell based assays but with a decreased potency and more limited selectivity compared to the enzyme assays.
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| http://dx.doi.org/10.1016/j.bmcl.2005.05.027 | DOI Listing |
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