AI Article Synopsis
- Researchers have identified the first non-substrate-like inhibitors for the enzyme PEPCK, which compete with GTP.
- The focus is on finding oral drugs to help manage glucose levels in Type 2 diabetes by reversibly inhibiting PEPCK.
- The compound 1-allyl-3-butyl-8-methylxanthine was modified, resulting in a 100-fold improvement in its effectiveness, contributing to the development of structure-activity relationship (SAR) insights for these inhibitors.
Article Abstract
The first non-substrate like inhibitors of human cytosolic phosphoenolpyruvate carboxykinase (PEPCK) competitive with GTP are reported. An effort to discover orally active compounds that improve glucose homeostasis in Type 2 diabetics by reversibly inhibiting PEPCK led to the discovery of 1-allyl-3-butyl-8-methylxanthine (5). We now report modifications at N-1 and C-8 that improved the in vitro activity of the initial xanthine HTS hit by 100-fold and a developing SAR for this class of inhibitor.
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| http://dx.doi.org/10.1016/s0960-894x(03)00722-4 | DOI Listing |
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