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

doi:10.1002/anie.201603797

Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging

Journal Article · Wed Jun 29 00:00:00 EDT 2016 · Angewandte Chemie (International Edition)

DOI:https://doi.org/10.1002/anie.201603797· OSTI ID:1400568

Liang, Steven H. ^[1]; Chen, Jinshan Michael ^[2]; Normandin, Marc D. ^[1]; Chang, Jeanne S. ^[2]; Chang, George C. ^[2]; Taylor, Christine K. ^[2]; Trapa, Patrick ^[3]; Plummer, Mark S. ^[2]; Para, Kimberly S. ^[2]; Conn, Edward L. ^[2]; Lopresti‐Morrow, Lori ^[2]; Lanyon, Lorraine F. ^[2]; Cook, James M. ^[2]; Richter, Karl E. G. ^[2]; Nolan, Charlie E. ^[2]; Schachter, Joel B. ^[2]; Janat, Fouad ^[2]; Che, Ye ^[2]; Shanmugasundaram, Veerabahu ^[2]; Lefker, Bruce A. ^[3] more »

Gordon Center for Medical Imaging &, Nuclear Medicine and Molecular Imaging Massachusetts General Hospital &, Department of Radiology Harvard Medical School Boston MA 02114 USA
Pfizer Worldwide Research and Development, Groton Laboratories Eastern Point Road Groton CT 06340 USA
Pfizer Worldwide Research and Development 610 Main Street Cambridge MA 02139 USA
Departments of Neurology &, Psychiatry Massachusetts General Hospital Harvard Medical School 185 Cambridge Street Boston MA 02114 USA
Stanley Center for Psychiatric Research Broad Institute 415 Main Street Cambridge MA o2142 USA
Stanley Center for Psychiatric Research Broad Institute 415 Main Street Cambridge MA o2142 USA, Departments of Neurology &, Psychiatry Massachusetts General Hospital Harvard Medical School 185 Cambridge Street Boston MA 02114 USA

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.

View Accepted Manuscript (Publisher)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1400568

Alternate ID(s):: OSTI ID: 1854169

Journal Information:: Angewandte Chemie (International Edition), Journal Name: Angewandte Chemie (International Edition) Journal Issue: 33 Vol. 55; ISSN 1433-7851

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: Germany

Language:: English

References (29)

GSK3β overexpression induces neuronal death and a depletion of the neurogenic niches in the dentate gyrus Sirerol-Piquer, MaSalomé; Gomez-Ramos, Pilar; Hernández, Félix Hippocampus https://doi.org/10.1002/hipo.20805	journal	January 2010
Molecular cloning and expression of glycogen synthase kinase-3/factor A. Woodgett, J. R. The EMBO Journal, Vol. 9, Issue 8 https://doi.org/10.1002/j.1460-2075.1990.tb07419.x	journal	August 1990
Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque: J. P. Holland Holland, Jason P.; Liang, Steven H.; Rotstein, Benjamin H. Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 57, Issue 4 https://doi.org/10.1002/jlcr.3158	journal	December 2013
Synthesis and ex vivo evaluation of carbon-11 labelled N-(4-methoxybenzyl)-N′-(5-nitro-1,3-thiazol-2-yl)urea ([11C]AR-A014418): A radiolabelled glycogen synthase kinase-3β specific inhibitor for PET studies Vasdev, Neil; Garcia, Armando; Stableford, Winston T. Bioorganic & Medicinal Chemistry Letters, Vol. 15, Issue 23 https://doi.org/10.1016/j.bmcl.2005.08.037	journal	December 2005
The first synthesis of [11C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3) Wang, Min; Gao, Mingzhang; Miller, Kathy D. Bioorganic & Medicinal Chemistry Letters, Vol. 21, Issue 1 https://doi.org/10.1016/j.bmcl.2010.11.026	journal	January 2011
Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas: Radiosynthesis of [11C-carbonyl] AR-A014418 by [11C]CO2 fixation Hicks, Justin W.; Wilson, Alan A.; Rubie, Elizabeth A. Bioorganic & Medicinal Chemistry Letters, Vol. 22, Issue 5 https://doi.org/10.1016/j.bmcl.2011.12.139	journal	March 2012
5-Aryl-4-carboxamide-1,3-oxazoles: Potent and selective GSK-3 inhibitors Gentile, Gabriella; Merlo, Giancarlo; Pozzan, Alfonso Bioorganic & Medicinal Chemistry Letters, Vol. 22, Issue 5 https://doi.org/10.1016/j.bmcl.2012.01.034	journal	March 2012
Radiosynthesis and preliminary PET evaluation of glycogen synthase kinase 3β (GSK-3β) inhibitors containing [11C]methylsulfanyl, [11C]methylsulfinyl or [11C]methylsulfonyl groups Kumata, Katsushi; Yui, Joji; Xie, Lin Bioorganic & Medicinal Chemistry Letters, Vol. 25, Issue 16 https://doi.org/10.1016/j.bmcl.2015.05.085	journal	August 2015
Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in Alzheimer's disease DaRocha-Souto, B.; Coma, M.; Pérez-Nievas, B. G. Neurobiology of Disease, Vol. 45, Issue 1 https://doi.org/10.1016/j.nbd.2011.09.002	journal	January 2012
Synthesis and evaluation of [11C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β) Cole, Erin L.; Shao, Xia; Sherman, Phillip Nuclear Medicine and Biology, Vol. 41, Issue 6 https://doi.org/10.1016/j.nucmedbio.2014.03.025	journal	July 2014
The glamour and gloom of glycogen synthase kinase-3 Jope, Richard S.; Johnson, Gail V. W. Trends in Biochemical Sciences, Vol. 29, Issue 2 https://doi.org/10.1016/j.tibs.2003.12.004	journal	February 2004
Pharmacological inhibitors of glycogen synthase kinase 3 Meijer, L.; Flajolet, M.; Greengard, P. Trends in Pharmacological Sciences, Vol. 25, Issue 9 https://doi.org/10.1016/j.tips.2004.07.006	journal	September 2004
Discovery of Isonicotinamides as Highly Selective, Brain Penetrable, and Orally Active Glycogen Synthase Kinase-3 Inhibitors Luo, Guanglin; Chen, Ling; Burton, Catherine R. Journal of Medicinal Chemistry, Vol. 59, Issue 3 https://doi.org/10.1021/acs.jmedchem.5b01550	journal	January 2016
Synthesis and Initial in Vivo Studies with [ ¹¹ C]SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3 Li, Lei; Shao, Xia; Cole, Erin L. ACS Medicinal Chemistry Letters, Vol. 6, Issue 5 https://doi.org/10.1021/acsmedchemlett.5b00044	journal	March 2015
Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties Wager, Travis T.; Hou, Xinjun; Verhoest, Patrick R. ACS Chemical Neuroscience, Vol. 1, Issue 6 https://doi.org/10.1021/cn100008c	journal	March 2010
GSK-3 modulates cellular responses to a broad spectrum of kinase inhibitors Thorne, Curtis A.; Wichaidit, Chonlarat; Coster, Adam D. Nature Chemical Biology, Vol. 11, Issue 1 https://doi.org/10.1038/nchembio.1690	journal	November 2014
GSK3 inhibitors: development and therapeutic potential Cohen, Philip; Goedert, Michel Nature Reviews Drug Discovery, Vol. 3, Issue 6 https://doi.org/10.1038/nrd1415	journal	June 2004
Tau in physiology and pathology Wang, Yipeng; Mandelkow, Eckhard Nature Reviews Neuroscience, Vol. 17, Issue 1 https://doi.org/10.1038/nrn.2015.1	journal	December 2015
Localization and Developmental Changes of τ Protein Kinase I/Glycogen Synthase Kinase-3β in Rat Brain Takahashi, Miho; Tomizawa, Kayoko; Kato, Rika Journal of Neurochemistry, Vol. 63, Issue 1 https://doi.org/10.1046/j.1471-4159.1994.63010245.x	journal	July 1994
Spatial learning deficit in transgenic mice that conditionally over-express GSK-3β in the brain but do not form tau filaments: Spatial learning deficit in Tet GSK-3β mice Hernández, Félix; Borrell, José; Guaza, Carmen Journal of Neurochemistry, Vol. 83, Issue 6 https://doi.org/10.1046/j.1471-4159.2002.01269.x	journal	December 2002
Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice Lucas, J. J. The EMBO Journal, Vol. 20, Issue 1 https://doi.org/10.1093/emboj/20.1.27	journal	January 2001
Increased level of active GSK-3? in Alzheimer's disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration Leroy, K.; Yilmaz, Z.; Brion, J. -P. Neuropathology and Applied Neurobiology, Vol. 33, Issue 1 https://doi.org/10.1111/j.1365-2990.2006.00795.x	journal	February 2007
The GSK3 hypothesis of Alzheimer’s disease: GSK3 and Alzheimer’s disease Hooper, Claudie; Killick, Richard; Lovestone, Simon Journal of Neurochemistry, Vol. 104, Issue 6 https://doi.org/10.1111/j.1471-4159.2007.05194.x	journal	December 2007
Glycogen synthase kinase-3 as drug target: From wallflower to center of attention Van Wauwe, J.; Haefner, B. Drug News & Perspectives, Vol. 16, Issue 9 https://doi.org/10.1358/dnp.2003.16.9.829337	journal	January 2003
Different Susceptibility to Neurodegeneration of Dorsal and Ventral Hippocampal Dentate Gyrus: A Study with Transgenic Mice Overexpressing GSK3β Fuster-Matanzo, Almudena; Llorens-Martín, María; de Barreda, Elena Gómez PLoS ONE, Vol. 6, Issue 11 https://doi.org/10.1371/journal.pone.0027262	journal	November 2011
Selectively Silencing GSK-3 Isoforms Reduces Plaques and Tangles in Mouse Models of Alzheimer's Disease Hurtado, D. E.; Molina-Porcel, L.; Carroll, J. C. Journal of Neuroscience, Vol. 32, Issue 21 https://doi.org/10.1523/JNEUROSCI.0889-12.2012	journal	May 2012
Lessons Learnt from Glycogen Synthase Kinase 3 Inhibitors Development for Alzheimer’s Disease Martinez, Ana; Perez, Daniel; Gil, Carmen Current Topics in Medicinal Chemistry, Vol. 13, Issue 15 https://doi.org/10.2174/15680266113139990138	journal	July 2013
Radiolabeled Small Molecule Protein Kinase Inhibitors for Imaging with PET or SPECT Hicks, Justin W.; VanBrocklin, Henry F.; Wilson, Alan A. Molecules, Vol. 15, Issue 11 https://doi.org/10.3390/molecules15118260	journal	November 2010
Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging Pandey, Mukesh K.; DeGrado, Timothy R. Theranostics, Vol. 6, Issue 4 https://doi.org/10.7150/thno.14334	journal	January 2016

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