title: CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism?
abstract: There are many challenges along the path to the approval of new drugs to treat CNS disorders, one of the greatest areas of unmet medical need with a large societal burden and health-care impact. Unfortunately, over the past two decades, few CNS drug approvals have succeeded, leading many pharmaceutical companies to deprioritize this therapeutic area. The reasons for the failures in CNS drug discovery are likely to be multifactorial. However, selecting the most biologically plausible molecular targets that are relevant to the disorder is a critical first step to improve the probability of success. In this review, we outline previous methods for identifying and validating novel targets for CNS drug discovery, and, cognizant of previous failures, we discuss potential new strategies that may improve the probability of success of developing novel treatments for CNS disorders.
authors: Neurobiology, CNS Discovery, Teva Pharmaceuticals, West Chester, Pennsylvania 19380; email: peter.hutson@tevapharm.com.
authors: P H
authors: PH
authors: Hutson
authors: Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20892; email: Janet.Clark@nih.gov.
authors: J A
authors: JA
authors: Clark
authors: Neuroscience Innovative Medicines, AstraZeneca, Cambridge, Massachusetts 01239; email: alan.cross@azneuro.com.
authors: A J
authors: AJ
authors: Cross
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods* / Q000592:standards*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D015203:Reproducibility of Results
chemical_list: D002491:Central Nervous System Agents
keywords: drug development; drug discovery; neurology; psychiatry; translational research