Discovery Chemistry & DMPK, H. Lundbeck A/S, Valby, Denmark.
Expert Opin Ther Pat. 2013 Jan;23(1):31-45. doi: 10.1517/13543776.2012.739157. Epub 2012 Dec 5.
Inhibitors of the phosphodiesterase enzyme PDE10A have been the target for extensive investigations and huge drug discovery research efforts during the recent years. Although PDE10A with its 13 years history is a relatively newly discovered target, it has been paradigmatic for the new generation of 'high efficiency drug discovery'. Several companies now have clinical programs aiming at validating the clinical potential of PDE10A inhibitors. The majority of companies have been focusing on the treatment of schizophrenia since preclinical evidence suggests that a PDE10A inhibitor could provide antipsychotic, pro-cognitive and negative symptom efficacy.
This article highlights and reviews research advances published in the patent literature since mid-2009 until mid-2012. The article is supplemented with selected publications from the scientific literature, emphasizing the possible involvement of PDE10A inhibitors in the treatment of schizophrenia.
Several compounds from various companies are currently undergoing clinical testing, dominated by compounds in clinical Phase I. Focus is mainly on CNS diseases and schizophrenia is the leading target indication.
近年来，磷酸二酯酶酶 10A（PDE10A）抑制剂一直是广泛研究和药物发现研究的目标。尽管 PDE10A 作为一个相对较新发现的靶点，已有 13 年的历史，但它是新一代“高效药物发现”的典范。目前，几家公司已经有了旨在验证 PDE10A 抑制剂临床潜力的临床项目。大多数公司一直专注于治疗精神分裂症，因为临床前证据表明 PDE10A 抑制剂可能具有抗精神病、认知促进和阴性症状的疗效。
本文重点介绍和回顾了自 2009 年年中至 2012 年年中发表在专利文献中的研究进展。文章还补充了来自科学文献的精选出版物，强调了 PDE10A 抑制剂可能在治疗精神分裂症中的作用。
目前，来自不同公司的几种化合物正在进行临床测试，以临床 I 期为主。重点主要集中在中枢神经系统疾病上，精神分裂症是主要的目标适应症。
