Pinard Emmanuel, Borroni Edilio, Koerner Annette, Umbricht Daniel, Alberati Daniela
Roche Pharmaceutical Research and Early Development (pRED) Roche Innovation Center Basel Medicinal Chemistry Department 124 Grenzacherstrasse, B 92 /6.30 CH-4070 Basel;, Email:
Roche Pharmaceutical Research and Early Development (pRED) Roche Innovation Center Basel Medicinal Chemistry Department 124 Grenzacherstrasse, B 92 /6.30 CH-4070 Basel.
Chimia (Aarau). 2018 Aug 22;72(7):477-484. doi: 10.2533/chimia.2018.477.
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.
甘氨酸转运体-1（GlyT1）抑制剂已在制药公司和学术机构中得到广泛研究，主要作为治疗精神分裂症（一种严重的慢性精神疾病）的潜在新方法。最近，临床前研究结果表明，这种方法对精神分裂症以外的中枢神经系统疾病以及非中枢神经系统适应症也可能具有治疗潜力。在过去的17年里，罗氏公司一直是GlyT1领域的关键参与者，发现并开发了比特普汀，这是迄今为止最先进的GlyT1抑制剂，也是唯一完成精神分裂症III期临床研究的药物。在本文中，我们讲述了比特普汀发现与开发的曲折历程，从2001年项目启动到如今在β地中海贫血（一种单基因遗传性血液疾病）患者中的评估。
