Peter Orth

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. ncbi request reprint Crystal structure of the catalytic domain of human ADAM33
    Peter Orth
    Schering Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    J Mol Biol 335:129-37. 2004
  2. doi request reprint Biaryl substituted hydantoin compounds as TACE inhibitors
    Wensheng Yu
    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:5286-9. 2010
  3. doi request reprint Discovery of novel spirocyclopropyl hydroxamate and carboxylate compounds as TACE inhibitors
    Zhuyan Guo
    Department of Chemistry, Schering Plough Research Institute, Kenilworth, NJ 07033 0539, USA
    Bioorg Med Chem Lett 19:54-7. 2009
  4. doi request reprint Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases
    Vinay M Girijavallabhan
    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:7283-7. 2010
  5. doi request reprint Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors: Part I--discovery of two binding modes
    Zhaoning Zhu
    Department of Medicinal Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 51:725-36. 2008
  6. doi request reprint Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody
    Brian M Beyer
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    J Mol Biol 382:942-55. 2008
  7. doi request reprint Discovery and SAR of hydantoin TACE inhibitors
    Wensheng Yu
    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:1877-80. 2010
  8. doi request reprint Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket
    Robert D Mazzola
    Department of Medicinal Chemistry, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 18:5809-14. 2008
  9. ncbi request reprint Structure and activity relationships of tartrate-based TACE inhibitors
    Dansu Li
    Department of Medicinal Chemistry, Merck Research Laboratories, Cambridge, 320 Bent Street, Cambridge, MA 02141, United States
    Bioorg Med Chem Lett 20:4812-5. 2010
  10. doi request reprint Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization
    Jared Cumming
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:2837-42. 2010

Collaborators

Detail Information

Publications13

  1. ncbi request reprint Crystal structure of the catalytic domain of human ADAM33
    Peter Orth
    Schering Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    J Mol Biol 335:129-37. 2004
    ..The substrate-binding site contains unique features that allow the structure-based design of specific inhibitors of this enzyme...
  2. doi request reprint Biaryl substituted hydantoin compounds as TACE inhibitors
    Wensheng Yu
    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:5286-9. 2010
    ..SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K(i), good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13...
  3. doi request reprint Discovery of novel spirocyclopropyl hydroxamate and carboxylate compounds as TACE inhibitors
    Zhuyan Guo
    Department of Chemistry, Schering Plough Research Institute, Kenilworth, NJ 07033 0539, USA
    Bioorg Med Chem Lett 19:54-7. 2009
    ..X-ray crystal structures and computer models of selected compounds binding to TACE explain the observed SAR. We report the first TACE X-ray crystal structure for an inhibitor with a carboxylate zinc ligand...
  4. doi request reprint Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases
    Vinay M Girijavallabhan
    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:7283-7. 2010
    ..These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles...
  5. doi request reprint Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors: Part I--discovery of two binding modes
    Zhaoning Zhu
    Department of Medicinal Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 51:725-36. 2008
    ..Mode A inhibitors occupy the S1'-S3' binding pockets, whereas mode B resides in the nonprime binding sites...
  6. doi request reprint Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody
    Brian M Beyer
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    J Mol Biol 382:942-55. 2008
    ..The binding site of the Fab is located exclusively on the p19 subunit, and comparison with published cytokine-receptor structures suggests that it overlaps with the IL-23 receptor binding site...
  7. doi request reprint Discovery and SAR of hydantoin TACE inhibitors
    Wensheng Yu
    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:1877-80. 2010
    ..SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand...
  8. doi request reprint Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket
    Robert D Mazzola
    Department of Medicinal Chemistry, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 18:5809-14. 2008
    ..X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1'-S3' pocket...
  9. ncbi request reprint Structure and activity relationships of tartrate-based TACE inhibitors
    Dansu Li
    Department of Medicinal Chemistry, Merck Research Laboratories, Cambridge, 320 Bent Street, Cambridge, MA 02141, United States
    Bioorg Med Chem Lett 20:4812-5. 2010
    ..The optimization of both the prime and non-prime sites led to compounds with picomolar activity. Several analogs demonstrated good rat pharmacokinetics...
  10. doi request reprint Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization
    Jared Cumming
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:2837-42. 2010
    ..Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Abeta(40) in transgenic mice with a single subcutaneous dose...
  11. ncbi request reprint IK682, a tight binding inhibitor of TACE
    Xiaoda Niu
    Department of Inflammation and Infection, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Arch Biochem Biophys 451:43-50. 2006
    ..The conformational changes of TACE may contribute significantly to the high affinity binding as a result of a more stable TACE-inhibitor complex...
  12. ncbi request reprint Stabilization of the autoproteolysis of TNF-alpha converting enzyme (TACE) results in a novel crystal form suitable for structure-based drug design studies
    Richard N Ingram
    Department of Structural Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Protein Eng Des Sel 19:155-61. 2006
    ..The characterization of this stabilized form of TACE has yielded an enzyme with similar native kinetic properties and identified a novel crystal form that is suitable for inhibitor soaking and structure determination...
  13. ncbi request reprint Crystallization and preliminary X-ray analysis of the acyl carrier protein synthase (AcpS) from Staphylococcus aureus
    Dayna L Daubaras
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    Acta Crystallogr D Biol Crystallogr 60:773-4. 2004
    ..The diffraction patterns of the crystals extend to 1.65 and 1.8 A, respectively. Full sets of X-ray diffraction data were collected from native crystals and the crystal structures were solved by molecular replacement...