Summary:

Protein tyrosine phosphatases (PTPs) are a large family of enzymes that remove a phosphoryl group from phosphotyrosyl (pY) proteins. A number of PTPs have been shown as viable targets for treatment of human diseases and conditions. For example, PTP1B inhibitors are expected to be effective therapeutics for type II diabetes and obesity.

SH2 domains are small modular domains found in a large number of signaling proteins. Their function is to bind to pY-containing proteins and promote protein-protein interactions. Inhibitors against SH2 domains have potential applications in treating cancer, osteoporosis, and inflammation, etc.

Because both proteins bind pY proteins as natural ligands, other investigators have developed a variety of pY mimetics which closely mimic the structure of pY. While some of them bind to PTPs and SH2 domains with high affinity, they are not membrane permeable due to their negative charge(s). In this invention, we have discovered a class of neutral molecules that bind reversibly to both PTPs and SH2 domains with high affinity and selectivity. Because the pY mimetic in this invention is neutral, inhibitors containing this core should have good membrane permeability and therefore offer a good lead for developing potent, selective PTP and SH2 inhibitors for therapeutic use.

Potential Applications:

Treatment of type II diabetes and obesity

Advantages:

• More selective inhibitor
• More potent