Publications by authors named "Mike Stashko"
Article Synopsis
- A novel series of oxalyl-aryl-amino benzoic acid-based inhibitors for PTP1B was developed.
- Using a solution phase parallel synthesis method, researchers quickly identified a potent inhibitor with a dissociation constant (K(i)) of 76 nM.
- The inhibitor showed moderate selectivity for PTP1B over TCPTP, acting by binding to a secondary phosphotyrosine site near the catalytic site.
Article Synopsis
- Protein Tyrosine phosphatase 1B (PTP1B) negatively regulates insulin and leptin signaling, making it a target for diabetes and obesity treatments.
- An NMR-based screening identified a compound, 2,3-dimethylphenyloxalylaminobenzoic acid, as a reversible and competitive inhibitor of PTP1B.
- Structure-based drug design led to the development of potent PTP1B inhibitors, with one compound showing promise by lowering plasma glucose levels in obese mice.
Glucocorticoids are potent anti-inflammatory and immunosuppressant agents. However, they also produce serious side effects that limit their usage. It has been proposed that anti-inflammatory properties of glucocorticoids are caused mostly by repression of activator protein 1- and nuclear factor kappabeta-stimulated synthesis of inflammatory mediators, whereas most of their adverse effects are associated with trans-activation of genes involved with metabolic processes.
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