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Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging.
Liang, Steven H; Chen, Jinshan Michael; Normandin, Marc D; Chang, Jeanne S; Chang, George C; Taylor, Christine K; Trapa, Patrick; Plummer, Mark S; Para, Kimberly S; Conn, Edward L; Lopresti-Morrow, Lori; Lanyon, Lorraine F; Cook, James M; Richter, Karl E G; Nolan, Charlie E; Schachter, Joel B; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Lefker, Bruce A; Enerson, Bradley E; Livni, Elijahu; Wang, Lu; Guehl, Nicolas J; Patnaik, Debasis; Wagner, Florence F; Perlis, Roy; Holson, Edward B; Haggarty, Stephen J; El Fakhri, Georges; Kurumbail, Ravi G; Vasdev, Neil.
Afiliação
  • Liang SH; Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
  • Chen JM; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Normandin MD; Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
  • Chang JS; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Chang GC; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Taylor CK; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Trapa P; Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA, 02139, USA.
  • Plummer MS; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Para KS; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Conn EL; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Lopresti-Morrow L; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Lanyon LF; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Cook JM; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Richter KE; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Nolan CE; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Schachter JB; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Janat F; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Che Y; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Shanmugasundaram V; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Lefker BA; Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA, 02139, USA.
  • Enerson BE; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.
  • Livni E; Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
  • Wang L; Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
  • Guehl NJ; Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
  • Patnaik D; Departments of Neurology & Psychiatry, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA, 02114, USA.
  • Wagner FF; Stanley Center for Psychiatric Research, Broad Institute, 415 Main Street, Cambridge, MA, o2142, USA.
  • Perlis R; Stanley Center for Psychiatric Research, Broad Institute, 415 Main Street, Cambridge, MA, o2142, USA.
  • Holson EB; Departments of Neurology & Psychiatry, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA, 02114, USA.
  • Haggarty SJ; Stanley Center for Psychiatric Research, Broad Institute, 415 Main Street, Cambridge, MA, o2142, USA.
  • El Fakhri G; Departments of Neurology & Psychiatry, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA, 02114, USA.
  • Kurumbail RG; Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.
  • Vasdev N; Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA. ravi.g.kurumbail@pfizer.com.
Angew Chem Int Ed Engl ; 55(33): 9601-5, 2016 08 08.
Article em En | MEDLINE | ID: mdl-27355874
ABSTRACT
Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A (11) C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxazóis / Triazóis / Encéfalo / Proteínas tau / Inibidores de Proteínas Quinases / Tomografia por Emissão de Pósitrons / Neuroimagem Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxazóis / Triazóis / Encéfalo / Proteínas tau / Inibidores de Proteínas Quinases / Tomografia por Emissão de Pósitrons / Neuroimagem Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article