Glycine Transporter Type I (GlyT1) Inhibitor, Bitopertin: A Journey from Lab to Patient.

Abstract

Glycine transporter-1 (GlyT1) inhibition has been extensively studied both in pharmaceutical companies and academic institutions primarily as a potential new approach to treat schizophrenia, a severe and chronic mental illness. More recently, preclinical results have suggested that this approach could also have therapeutic potential for CNS disorders beyond schizophrenia as well as for non-CNS indications. Over the past 17 years, Roche has been a key player in the GlyT1 field with the discovery and development of bitopertin, the most advanced GlyT1 inhibitor to date and the only one which completed Phase III clinical studies for schizophrenia. In this article, we relate the eventful journey of the discovery and development of bitopertin, from project initiation in 2001 to its evaluation today in patients suffering from beta-thalassemia, a monogenic hereditary haematological disorder.

• Authors: Emmanuel Pinard, Edilio Borroni, Annette Koerner, Daniel Umbricht, Daniela Alberati
• Journal: Chimia (Chimia (Aarau)) Vol. 72 Issue 7 Pg. 477-484 (Aug 22 2018) ISSN: 0009-4293 [Print] Switzerland
• PMID: 30158010 (Publication Type: Journal Article)

Chemical References

• (4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
• Glycine Plasma Membrane Transport Proteins
• Piperazines
• SLC6A9 protein, human
• Sulfones

Topics

• Animals
• Drug Development
• Drug Discovery
• Glycine Plasma Membrane Transport Proteins (antagonists & inhibitors)
• High-Throughput Screening Assays
• Humans
• Piperazines (pharmacology, therapeutic use)
• Schizophrenia (drug therapy)
• Sulfones (pharmacology, therapeutic use)
• beta-Thalassemia (drug therapy)