title: Designing drugs with multi-target activity: the next step in the treatment of neurodegenerative disorders.
abstract: BACKGROUND
  Neurodegenerative diseases have had devastating effects on patients' quality of life. These complex diseases have several pathways that are affected to initiate cell death. Current therapies, designed to address only a single target, fall short in mitigating or preventing disease progression, and disease-modifying drugs are desperately needed. Over the past several years, a new paradigm has emerged which has as a goal the targeting of multiple disease etiological pathways. Such "multi-targeted designed drugs" (MTDD) have shown great promise in preclinical studies as neuroprotective agents, as well as being able to afford symptomatic relief to blunt the day-to-day burden of these illnesses.
  
  
  METHODS
  In this review, the authors evaluate the use of chemical scaffolds that led themselves exquisitely to the development of MTDDs in central nervous system disorders. Some of the examples discussed have also transitioned into the clinic, which underscores the importance of pursuing drug discovery programs within the multifunctional arena.
  
  
  CONCLUSIONS
  Currently, very little can be done to slow the progress of neurodegeneration. The multifaceted profile of neurodegeneration necessitates a change in paradigm toward the design of compounds that address several drug targets simultaneously. With successful compounds in clinical trials as well as compounds moving into the clinic, support is growing and the feasibility of this approach is now becoming recognized. This review shows that several small molecule scaffolds can be successfully utilized to design MTDD compounds with good CNS pharmacokinetics.
authors.affiliation: Northeast Ohio Medical University, College of Pharmacy, Neurotherapeutics Emphasis Group, Department of Pharmaceutical Sciences, Rootstown, 4209 State Route 44, P.O. Box 95, OH 44272, USA.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Geldenhuys
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Van der Schyf
mesh_terms: D002493:Central Nervous System Diseases / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents