Diabetes R D Pipeline: 11beta-HSD1 Inhibitors

Summary

11beta-HSD1 (11beta-hydroxysteroid dehydrogenase type 1) antagonists are insulin sensitizers. 11beta-HSD1 is surely an enzyme that converts inactive cortisone into potent, biologically active hormone, cortisol. This conversion occurs within cells of key metabolic tissues including liver, adipose tissue, muscle tissue, and pancreas. Cortisol elevates blood glucose levels by increasing glucose production in liver, and by inhibiting uptake and disposal of glucose in muscle and adipose tissues. Consequently, 11beta-HSD1 mediated output of cortisol contributes to insulin resistance, development of type 2 diabetes, and associated cardiovascular diseases

Preclinical reports have demonstrated that transgenic mice overexpressing 11beta-HSD1-selectively in adipose tissue develop type 2 diabetes and visceral obesity, when compared with 11beta-HSD1 knockout mouse, which displays normoglycemia and normal weight.

11beta-HSD1 inhibitors were found to improve insulin sensitivity and glucose tolerance also to have anti-obesity effects. In addition, atherosclerotic plaques in apoE knockout mice were improved after treatment with 11beta- HSD1 inhibitors.

11beta-HSD1 inhibitors look like attractive research and development products for your treatment of diabetes type 2 symptoms because a large number of major biotechnology and pharmaceutical companies take part in their development, which pipeline, although very young, already has 70% of merchandise in clinical stage of development.

Analysis reveals that total of 10 products based on 11beta-HSD1 inhibitors are undergoing development for your treatment of diabetes by 10 companies. Seven away from 11 companies discounted test strips are major biotechnology and pharmaceutical companies. In addition, at least eight more companies are involved in progression of 11beta-HSD1 inhibitors. Majority (70%) of 11beta-HSD1 inhibitors come in Phase I many studies. Roche Holding, Ltd. (Switzerland) domineers with this field. All 6 US patents covering 11beta-HSD1 inhibitors, issued to date, holds Hoffman-La Roche, Inc. (USA), a small business unit of Roche Holding, Ltd.

(Switzerland). Out of 15 applications for 11beta-HSD1 inhibitors, registered with the US Patent Office, 11 are part of Hoffman-La Roche, Inc. (USA). So far, growth and development of three 11 beta-HSD1 inhibitors was terminated, including DIO-902 in April 2009, due to the termination of DiObex, Inc. (USA) business activities, INCB 20817 in 2008 (substituted for and INCB13739) and PF-915275 (N-(Pyridin-2-yl) arylsulfonamide inhibitor of i11beta-HSD1) in 2007 (without explanation). In addition, the USA Phase II clinical study with JTT-654 was terminated 3 months after its start.

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