Identification of Chemical Lead Structures

To identify small molecule PTP lead structures, the most straightforward method is to mimic the natural substrate pTyr by making non-hydrolyzable analogs. Initial attempts in academia were very successful in developing model compounds as described below (Sect. 9.1). Since these compounds often showed poor or no cellular activity, most companies turned to high-throughput screening (HTS) in attempts to identify novel lead structures. At Novo Nordisk we used a scintillation proximity assay (SPA) with PTP1B and a biotinylated [33P]-radiolabeled peptide substrate corresponding to the activation loop of the insulin receptor tyrosine kinase. A substantial number of hits were identified in the screening. However, when analyzing these hit compounds in detail, as recommended below, most were eliminated as false positives. The compound that fulfilled most of our pre-defined selection criteria (see below) was 2-(oxalylamino)-benzoic acid, OBA (compound 1, Fig. 4; Andersen et al. 2000). This compound was found to share most of the

Fig. 4 Chemical lead structures identified by different strategies
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment