Journal of Diabetes & Metabolism

ISSN - 2155-6156

Development of HSD-016 and HSD-621 as potential agents for the treatment of type 2 diabetes

4th World Congress on Diabetes & Metabolism

August 14-16, 2013 Holiday Inn Chicago-North Shore, IL, USA

Zhao Kui Wan

Scientific Tracks Abstracts: J Diabetes Metab

Abstract :

The glucocorticoid receptor (GR) signaling pathway has been linked to the pathophysiology of diabetes and metabolic syndrome. We developed a series of potent and selective 11β-HSD1 inhibitors. These compounds showed excellent potency against both human and mouse 11β-HSD1 enzymes and displayed good pharmacokinetics and ex vivo inhibition of the target in mice.Compounds HSD-016 and HSD-621 were ultimately selected as clinical development candidates. Both compounds have attractive overall pharmaceutical profiles and demonstrated good oral bioavailability in mouse, rat and dog. When orally dosed in C57/BL6 diet-induced-obesity (DIO) mice, HSD-016 and HSD-621 were efficacious and showed a significant reduction in both fed and fasting glucose and insulin levels. Furthermore, both compoundswere well tolerated in drug safety assessment studies.

Biography :

Zhao Kui Wan received his Ph.D. degree from Boston University and conducted postdoctoral research at Harvard University where he discovered the sulfonamide-based ligand for asymmetric Nozaki-Hiyama-Kishi Reactions under the guidance of Prof. Yoshito Kishi. Also at Harvard, he developed a practical synthesis of a key fragment of Eribulin that is now approved for the treatment of breast cancer under the name of HalavenTM. As a medicinal chemist, his research has experience in the fields of metabolic and inflammatory diseases. He played a key role in the development of two clinical and pre-clinical candidates for Type II diabetes. He also developed a novel and efficient phosphonium-mediated and related bond forming reactions in heterocyclic systems arising from serendipitous observations. He has nearly has near 70 scientific publications in peer-reviewed journals, patents and meeting abstracts. He is an ad hoc reviewer for almost a dozen prestigious scientific journals and serves on the Editorial board for North American Journal of Medicine & Health. He was a co-founder of Chinese BioMedical Association (CABA) and served as the President (2009- 2010). He was a Young Industrial Investigator (the American Chemistry Society, Division of Organic Chemistry and Diversion of Medicinal Chemistry, 2008).