Jonathan C Cruz

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles
    Jonathan C Cruz
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Neuron 40:471-83. 2003
  2. ncbi request reprint A Jekyll and Hyde kinase: roles for Cdk5 in brain development and disease
    Jonathan C Cruz
    Department of Pathology, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts, 02115 USA
    Curr Opin Neurobiol 14:390-4. 2004
  3. ncbi request reprint Cdk5 deregulation in the pathogenesis of Alzheimer's disease
    Jonathan C Cruz
    Department of Pathology, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Trends Mol Med 10:452-8. 2004
  4. doi request reprint SAR profiles of spirocyclic nicotinamide derived selective HDAC1/HDAC2 inhibitors (SHI-1:2)
    Joey L Methot
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 18:6104-9. 2008
  5. doi request reprint Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization
    Solomon D Kattar
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 19:1168-72. 2009
  6. doi request reprint Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1)
    Kevin J Wilson
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 18:1859-63. 2008
  7. ncbi request reprint p25/cyclin-dependent kinase 5 induces production and intraneuronal accumulation of amyloid beta in vivo
    Jonathan C Cruz
    Department of Pathology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    J Neurosci 26:10536-41. 2006
  8. doi request reprint Purine derivatives as potent gamma-secretase modulators
    Alexey Rivkin
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 20:2279-82. 2010
  9. doi request reprint Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2)
    Joey L Methot
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 18:973-8. 2008
  10. doi request reprint Fluorinated piperidine acetic acids as gamma-secretase modulators
    Matthew G Stanton
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 20:755-8. 2010

Research Grants

  1. Role of Cdk5 in Phosphorylating Alzheimer's APP
    Jonathan Cruz; Fiscal Year: 2004

Collaborators

Detail Information

Publications13

  1. ncbi request reprint Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles
    Jonathan C Cruz
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Neuron 40:471-83. 2003
    ..Our cumulative findings provide compelling evidence that in vivo deregulation of Cdk5 by p25 plays a causative role in neurodegeneration and the development of neurofibrillary pathology...
  2. ncbi request reprint A Jekyll and Hyde kinase: roles for Cdk5 in brain development and disease
    Jonathan C Cruz
    Department of Pathology, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts, 02115 USA
    Curr Opin Neurobiol 14:390-4. 2004
    ....
  3. ncbi request reprint Cdk5 deregulation in the pathogenesis of Alzheimer's disease
    Jonathan C Cruz
    Department of Pathology, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Trends Mol Med 10:452-8. 2004
  4. doi request reprint SAR profiles of spirocyclic nicotinamide derived selective HDAC1/HDAC2 inhibitors (SHI-1:2)
    Joey L Methot
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 18:6104-9. 2008
    ..Compound 12 induced a 4-fold increase in acetylated histone H2B in an HCT-116 xenograft model study with acute exposure, and inhibited tumor growth in a 21-day efficacy study with qd dosing...
  5. doi request reprint Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization
    Solomon D Kattar
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 19:1168-72. 2009
    ..Advanced compounds were the culmination of iterative library design and possess excellent biochemical and cellular potency, as well as acceptable PK and efficacy in animal models...
  6. doi request reprint Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1)
    Kevin J Wilson
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 18:1859-63. 2008
    ..Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog...
  7. ncbi request reprint p25/cyclin-dependent kinase 5 induces production and intraneuronal accumulation of amyloid beta in vivo
    Jonathan C Cruz
    Department of Pathology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    J Neurosci 26:10536-41. 2006
    ..Collectively, these findings delineate a novel pathological mechanism involving aberrant APP processing by p25/Cdk5 and have important implications in AD pathogenesis...
  8. doi request reprint Purine derivatives as potent gamma-secretase modulators
    Alexey Rivkin
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 20:2279-82. 2010
    ....
  9. doi request reprint Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2)
    Joey L Methot
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 18:973-8. 2008
    ..Based on the SAR of these agents and our current understanding of the HDAC active site, we postulate that the SHI-1:2 extend the existing HDAC inhibitor pharmacophore to include an internal binding domain...
  10. doi request reprint Fluorinated piperidine acetic acids as gamma-secretase modulators
    Matthew G Stanton
    Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 20:755-8. 2010
    ..Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects...
  11. doi request reprint Triazoles as γ-secretase modulators
    Christian Fischer
    Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 21:4083-7. 2011
    ..1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of γ-secretase activity, excellent pharmacokinetics and good central lowering of Aβ42 in Sprague-Dawley rats...
  12. ncbi request reprint The discovery of 6-amino nicotinamides as potent and selective histone deacetylase inhibitors
    Christopher L Hamblett
    Department of Drug Design and Optimization Medicinal Chemistry, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
    Bioorg Med Chem Lett 17:5300-9. 2007
    ....
  13. ncbi request reprint Niemann-Pick type C disease and intracellular cholesterol trafficking
    Ta Yuan Chang
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 280:20917-20. 2005

Research Grants1

  1. Role of Cdk5 in Phosphorylating Alzheimer's APP
    Jonathan Cruz; Fiscal Year: 2004
    ..Finally, the proposed work may aid in developing benign and effective pharmacological agents as potential drug therapies for AD by specifically blocking the formation or activity of p25/Cdk5. ..