V Madison

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. pmc Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034
    Vincent Madison
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Synchrotron Radiat 15:204-7. 2008
  2. ncbi request reprint Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors
    V Madison
    Department of Structural Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Biophys Chem 101:239-47. 2002
  3. pmc Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease
    X Tong
    Department of Virology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Antimicrob Agents Chemother 54:2365-70. 2010
  4. ncbi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency
    S Bogen
    Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4515-9. 2005
  5. ncbi request reprint Effect of naturally occurring active site mutations on hepatitis C virus NS3 protease specificity
    B M Beyer
    Department of Structural Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    Proteins 43:82-8. 2001
  6. ncbi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency
    A Arasappan
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4180-4. 2005
  7. ncbi request reprint Expression, purification, characterization and homology modeling of active Akt/PKB, a key enzyme involved in cell survival signaling
    C C Kumar
    Department of Tumor Biology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Biochim Biophys Acta 1526:257-68. 2001
  8. ncbi request reprint Improving tolerance of Candida antarctica lipase B towards irreversible thermal inactivation through directed evolution
    Ningyan Zhang
    Biotransformations Group and Structure Chemistry, Schering Plough Research Institute, U 13 3000, 1011 Morris Avenue, Union, NJ 07083, USA
    Protein Eng 16:599-605. 2003
  9. 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
  10. ncbi request reprint P2-P4 macrocyclic inhibitors of hepatitis C virus NS3-4A serine protease
    Ashok Arasappan
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 16:3960-5. 2006

Detail Information

Publications32

  1. pmc Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034
    Vincent Madison
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Synchrotron Radiat 15:204-7. 2008
    ..This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease, which is currently in clinical trials...
  2. ncbi request reprint Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors
    V Madison
    Department of Structural Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Biophys Chem 101:239-47. 2002
    ..Even though potent inhibitors of PDF have been discovered, their bacteriostatic mechanism of action and the rapid development of resistance in vitro may limit their potential as antibacterial drugs...
  3. pmc Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease
    X Tong
    Department of Virology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Antimicrob Agents Chemother 54:2365-70. 2010
    ..In summary, the results of the preclinical characterization of the antiviral activity of SCH 900518 support its evaluation in clinical studies...
  4. ncbi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency
    S Bogen
    Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4515-9. 2005
    ..Modification of the P(2) and P(1) side chains of earlier P(3)-capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 resulted in the discovery of compound 24 with about 10-fold improvement in potency...
  5. ncbi request reprint Effect of naturally occurring active site mutations on hepatitis C virus NS3 protease specificity
    B M Beyer
    Department of Structural Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    Proteins 43:82-8. 2001
    ..Modeling these unnatural substrate/mutant protease interactions, on the basis of cocrystal structures of enzyme-substrate complexes, provides a structural basis for these observations. Proteins 2001;43:82-88...
  6. ncbi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency
    A Arasappan
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4180-4. 2005
    ..X-ray crystal structure of one of the inhibitors (43) bound to the protease revealed the importance of the P'2 moiety...
  7. ncbi request reprint Expression, purification, characterization and homology modeling of active Akt/PKB, a key enzyme involved in cell survival signaling
    C C Kumar
    Department of Tumor Biology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Biochim Biophys Acta 1526:257-68. 2001
    ..However, the ATP binding regions are highly conserved in the three isoforms of Akt implying that the discovery of isoform-selective inhibitors would be very challenging...
  8. ncbi request reprint Improving tolerance of Candida antarctica lipase B towards irreversible thermal inactivation through directed evolution
    Ningyan Zhang
    Biotransformations Group and Structure Chemistry, Schering Plough Research Institute, U 13 3000, 1011 Morris Avenue, Union, NJ 07083, USA
    Protein Eng 16:599-605. 2003
    ..The catalytic efficiency of the mutants with p-nitrophenyl butyrate and 6,8-difluoro-4-methylumbelliferyl octanoate was also found to be superior to that of WT-CALB...
  9. 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...
  10. ncbi request reprint P2-P4 macrocyclic inhibitors of hepatitis C virus NS3-4A serine protease
    Ashok Arasappan
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 16:3960-5. 2006
    ..X-ray structure of inhibitor 38 bound to the protease is discussed...
  11. ncbi request reprint Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavaila
    Srikanth Venkatraman
    Schering Plough Research Institute, K 15, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 49:6074-86. 2006
    ..X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed...
  12. ncbi request reprint Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II.
    Andrew J Prongay
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 50:2310-8. 2007
    ..B 1970, 257, 249-264]. This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease that is currently in clinical trials...
  13. ncbi request reprint Versatile templates for the development of novel kinase inhibitors: Discovery of novel CDK inhibitors
    Michael P Dwyer
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 17:6216-9. 2007
    ..From the in-vitro and cell-based analysis, the pyrazolo[1,5-a]pyrimidine core (represented by 9) emerged as the superior core for further elaboration in the identification of novel CDK2 inhibitors...
  14. ncbi request reprint Pyrazolo[1,5-a]pyrimidines as orally available inhibitors of cyclin-dependent kinase 2
    Kamil Paruch
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 17:6220-3. 2007
    ..Properly substituted pyrazolo[1,5-a]pyrimidines are potent and selective CDK2 inhibitors. Compound 15j is orally available and showed efficacy in a mouse A2780 xenograft model...
  15. ncbi request reprint Structure-guided discovery of cyclin-dependent kinase inhibitors
    Thierry O Fischmann
    Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Biopolymers 89:372-9. 2008
    ..Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity...
  16. 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...
  17. doi request reprint Construction and characterization of a fully active PXR/SRC-1 tethered protein with increased stability
    Wenyan Wang
    Structural Chemistry Department, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Protein Eng Des Sel 21:425-33. 2008
    ....
  18. 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...
  19. ncbi request reprint Novel potent hepatitis C virus NS3 serine protease inhibitors derived from proline-based macrocycles
    Kevin X Chen
    Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
    J Med Chem 49:995-1005. 2006
    ..The strategy of macrocyclization has been proved to be successful in improving potency (>20-fold greater than that of 1) and in structural depeptization...
  20. ncbi request reprint Impact of naturally occurring variants of HCV protease on the binding of different classes of protease inhibitors
    Xiao Tong
    Antiviral Therapy, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Biochemistry 45:1353-61. 2006
    ..The identification of naturally occurring variations which can affect inhibitor binding is an important step in the design of broad-spectrum, second generation protease inhibitors...
  21. ncbi request reprint Application of the lambda-dynamics method to evaluate the relative binding free energies of inhibitors to HCV protease
    Zhuyan Guo
    Department of Structural Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 46:5360-4. 2003
    ..The fact that the lambda-dynamics method achieved similar results in only a fraction of the total simulation time for FEP further demonstrates the robustness of the lambda-dynamics method...
  22. 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...
  23. pmc Three-dimensional models of wild-type and mutated forms of cytochrome P450 14alpha-sterol demethylases from Aspergillus fumigatus and Candida albicans provide insights into posaconazole binding
    Li Xiao
    Department of Structural Chemistry, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Antimicrob Agents Chemother 48:568-74. 2004
    ..The model also predicts that mutations that were previously shown to specifically impact POS susceptibility in A. fumigatus and C. albicans act by interfering with the binding of the long side chain...
  24. ncbi request reprint Improved activity and thermostability of Candida antarctica lipase B by DNA family shuffling
    Wen Chen Suen
    Biotransformations Group, Schering Plough Research Institute, Union, NJ 07083, USA
    Protein Eng Des Sel 17:133-40. 2004
    ..antarctica ATCC 32657 by 11-fold and 6.4 degrees C, respectively, which closely approached the stability characteristics of the most thermostable parent derived from Hyphozyma sp. CBS 648.91...
  25. ncbi request reprint ADAM33 enzyme properties and substrate specificity
    Jun Zou
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    Biochemistry 44:4247-56. 2005
    ..ADAM33 dependence on buffer conditions, detergents, and temperature was examined, and optimal conditions were defined. Accurate K(i) values for tissue inhibitors of metalloproteinase and small molecule compounds were obtained...
  26. ncbi request reprint Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease
    Kevin X Chen
    Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4475-8. 2005
    ..The macrocyclic alpha-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters...
  27. pmc Human members of the eukaryotic protein kinase family
    Mitch Kostich
    Discovery Technology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Genome Biol 3:RESEARCH0043. 2002
    ..Near completion of projects to sequence the human genome and transcriptome provide an opportunity to identify and perform sequence analysis on a nearly complete set of human EPKs...
  28. ncbi request reprint Design, synthesis, and biological activity of m-tyrosine-based 16- and 17-membered macrocyclic inhibitors of hepatitis C virus NS3 serine protease
    Kevin X Chen
    Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, New Jersey 07033, USA
    J Med Chem 48:6229-35. 2005
    ..P2' phenyl and P1 propyl groups wrapped around the Lys136 side chain, forming a "C"-shaped clamp. The 17-membered macrocyclic inhibitors 17-19 were significantly more potent than the acyclic pentapeptide 1...
  29. ncbi request reprint Proline-based macrocyclic inhibitors of the hepatitis C virus: stereoselective synthesis and biological activity
    Kevin X Chen
    Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, NJ 07033, USA
    Angew Chem Int Ed Engl 44:7024-8. 2005
  30. ncbi request reprint Insights from a three-dimensional model into ligand binding to constitutive active receptor
    Li Xiao
    Department of Structural Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    Drug Metab Dispos 30:951-6. 2002
    ..The results from this study indicate that structural modeling will be a useful tool for understanding ligand binding to hCAR and for design of drugs free of hCAR-mediated enzyme induction...
  31. ncbi request reprint Potent 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-based macrocyclic inhibitors of hepatitis C virus NS3 protease
    Kevin X Chen
    Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Med Chem 49:567-74. 2006
    ..The ketone carbonyl formed a reversible covalent bond with Ser139. The n-propyl of P1 novaline and the aromatic ring of P2' phenylglycine formed a C-shaped clamp around the Lys136 side chain...
  32. ncbi request reprint AKT crystal structure and AKT-specific inhibitors
    Chandra C Kumar
    Department of Tumor Biology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Oncogene 24:7493-501. 2005
    ..The issues and challenges facing the development of different classes of inhibitors as therapeutics are also discussed...