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Novel therapeutic modalities to address nondrugable protein interaction targets.
De Souza, Errol B; Cload, Sharon T; Pendergrast, Patrick Shannon; Sah, Dinah W Y.
Afiliación
  • De Souza EB; Archemix Corporation, Cambridge, MA 02142, USA. edesouza@archemix.com
Neuropsychopharmacology ; 34(1): 142-58, 2009 Jan.
Article en En | MEDLINE | ID: mdl-18754007
Small molecule drugs are relatively effective in working on 'drugable' targets such as GPCRs, ion channels, kinases, proteases, etc but ineffective at blocking protein-protein interactions that represent an emerging class of 'nondrugable' central nervous system (CNS) targets. This article provides an overview of novel therapeutic modalities such as biologics (in particular antibodies) and emerging oligonucleotide therapeutics such as antisense, small-interfering RNA, and aptamers. Their key properties, overall strengths and limitations, and their utility as tools for target validation are presented. In addition, issues with regard to CNS targets as it relates to the blood-brain barrier penetration are discussed. Finally, examples of their application as therapeutics for the treatment of pain and some neurological disorders such as Alzheimer's disease, multiple sclerosis, Huntington's disease, and Parkinson's disease are provided.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos del Sistema Nervioso Central / Enfermedades del Sistema Nervioso Central / Sistemas de Liberación de Medicamentos / Dominios y Motivos de Interacción de Proteínas Límite: Animals / Humans Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos del Sistema Nervioso Central / Enfermedades del Sistema Nervioso Central / Sistemas de Liberación de Medicamentos / Dominios y Motivos de Interacción de Proteínas Límite: Animals / Humans Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido