Walter Huber

Summary

Affiliation: F. Hoffmann-La Roche Ltd

Publications

  1. ncbi request reprint Predicting plasma protein binding of drugs: a new approach
    Nicole A Kratochwil
    Chemical Technologies, F Hoffmann La Roche, CH 4070, Basel, Switzerland
    Biochem Pharmacol 64:1355-74. 2002
  2. ncbi request reprint Predicting plasma protein binding of drugs--revisited
    Nicole A Kratochwil
    Department of Discovery Chemistry, F Hoffmann La Roche, CH 4070 Basel, Switzerland
    Curr Opin Drug Discov Devel 7:507-12. 2004
  3. ncbi request reprint SPR-based interaction studies with small molecular weight ligands using hAGT fusion proteins
    Walter Huber
    F Hoffmann La Roche Ltd, Pharmaceutical Research, Discovery Chemistry, CH 4070 Basel, Switzerland
    Anal Biochem 333:280-8. 2004
  4. ncbi request reprint Biomolecular interaction analysis in drug discovery using surface plasmon resonance technology
    Walter Huber
    F Hoffmann La Roche AG, Department of Pharma Research, CH 4070 Basel, Switzerland
    Curr Pharm Des 12:3999-4021. 2006
  5. ncbi request reprint Thermodynamic studies on the interaction of antibodies with beta-amyloid peptide
    Manfred Brockhaus
    Department PRBD, F Hoffmann La Roche Ltd, CH 4070 Basel, Switzerland, and Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    J Phys Chem B 111:1238-43. 2007
  6. ncbi request reprint A new strategy for improved secondary screening and lead optimization using high-resolution SPR characterization of compound-target interactions
    Walter Huber
    F Hoffman La Roche Ltd, Pharmaceutical Research, Discovery Chemistry, Basel, Switzerland
    J Mol Recognit 18:273-81. 2005
  7. doi request reprint Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes
    Eric Kitas
    F Hoffmann La Roche Ltd, Discovery Research Basel, CH 4070 Basel, Switzerland
    Bioorg Med Chem Lett 20:594-9. 2010
  8. doi request reprint Fragment-based screening using surface plasmon resonance technology
    Samantha Perspicace
    F Hoffmann La Roche Ltd, Pharma Research, Discovery Technologies, Basel, Switzerland
    J Biomol Screen 14:337-49. 2009
  9. pmc Generation, characterization and structural data of chymase binding proteins based on the human Fyn kinase SH3 domain
    Daniel Schlatter
    F Hoffmann La Roche Ltd, Pharma Research and Early Development, Discovery Technologies, Basel, Switzerland
    MAbs 4:497-508. 2012
  10. ncbi request reprint Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2
    Christophe Dhalluin
    F Hoffmann La Roche AG, Department of Pharma Research, CH 4070 Basel, Switzerland
    Bioconjug Chem 16:518-27. 2005

Collaborators

Detail Information

Publications20

  1. ncbi request reprint Predicting plasma protein binding of drugs: a new approach
    Nicole A Kratochwil
    Chemical Technologies, F Hoffmann La Roche, CH 4070, Basel, Switzerland
    Biochem Pharmacol 64:1355-74. 2002
    ..99% plasma protein binding. Depending on the system, this can be important in medicinal chemistry programs and may together with other computed physicochemical and ADME properties assist in the prioritization of synthetic strategies...
  2. ncbi request reprint Predicting plasma protein binding of drugs--revisited
    Nicole A Kratochwil
    Department of Discovery Chemistry, F Hoffmann La Roche, CH 4070 Basel, Switzerland
    Curr Opin Drug Discov Devel 7:507-12. 2004
    ..The issue of why it is difficult to achieve prediction of sufficient quality for a diverse dataset will also be considered...
  3. ncbi request reprint SPR-based interaction studies with small molecular weight ligands using hAGT fusion proteins
    Walter Huber
    F Hoffmann La Roche Ltd, Pharmaceutical Research, Discovery Chemistry, CH 4070 Basel, Switzerland
    Anal Biochem 333:280-8. 2004
    ..The K(D) value is in excellent agreement with the K(D) value determined in solution by fluorescence titration...
  4. ncbi request reprint Biomolecular interaction analysis in drug discovery using surface plasmon resonance technology
    Walter Huber
    F Hoffmann La Roche AG, Department of Pharma Research, CH 4070 Basel, Switzerland
    Curr Pharm Des 12:3999-4021. 2006
    ..This information can be directly used to improve binding properties of a drug candidate...
  5. ncbi request reprint Thermodynamic studies on the interaction of antibodies with beta-amyloid peptide
    Manfred Brockhaus
    Department PRBD, F Hoffmann La Roche Ltd, CH 4070 Basel, Switzerland, and Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    J Phys Chem B 111:1238-43. 2007
    ..DeltaC(0)(p, abeta) was large and negative but could not be explained exclusively by the hydrophobic effect. The free energy of binding was found to be linearly correlated with the size of the epitope...
  6. ncbi request reprint A new strategy for improved secondary screening and lead optimization using high-resolution SPR characterization of compound-target interactions
    Walter Huber
    F Hoffman La Roche Ltd, Pharmaceutical Research, Discovery Chemistry, Basel, Switzerland
    J Mol Recognit 18:273-81. 2005
    ..Here, we present three examples of how this technique can be applied to provide invaluable data during different phases of the drug discovery process...
  7. doi request reprint Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes
    Eric Kitas
    F Hoffmann La Roche Ltd, Discovery Research Basel, CH 4070 Basel, Switzerland
    Bioorg Med Chem Lett 20:594-9. 2010
    ..Compound 12 showed favorable ADME properties, for example, F=70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes...
  8. doi request reprint Fragment-based screening using surface plasmon resonance technology
    Samantha Perspicace
    F Hoffmann La Roche Ltd, Pharma Research, Discovery Technologies, Basel, Switzerland
    J Biomol Screen 14:337-49. 2009
    ..These results validate the authors' library and demonstrate that the application of SPR technology as a filter in fragment screening can be achieved successfully...
  9. pmc Generation, characterization and structural data of chymase binding proteins based on the human Fyn kinase SH3 domain
    Daniel Schlatter
    F Hoffmann La Roche Ltd, Pharma Research and Early Development, Discovery Technologies, Basel, Switzerland
    MAbs 4:497-508. 2012
    ..Finally, their highly specific inhibitory activity and favorable molecular properties support the use of Fynomers as potential therapeutic agents...
  10. ncbi request reprint Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2
    Christophe Dhalluin
    F Hoffmann La Roche AG, Department of Pharma Research, CH 4070 Basel, Switzerland
    Bioconjug Chem 16:518-27. 2005
    ..This study constitutes an essential collection of knowledge on which the interaction of (40)PEG-IFNalpha(2a) and its positional isomers with its cellular receptors can be better understood...
  11. doi request reprint Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites
    Paul Hebeisen
    F Hoffmann La Roche Ltd, Discovery Research Basel, CH 4070 Basel, Switzerland
    Bioorg Med Chem Lett 18:4708-12. 2008
    ..By bridging two adjacent allosteric binding sites using two aromatic sulfonylureas as anchor units and covalently linking them, it was possible to obtain dual binding AMP site inhibitors that exhibit a strong inhibitory effect...
  12. ncbi request reprint Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV
    Ralf Thoma
    F Hoffmann La Roche AG, Pharma Research Discovery, 4070 Basel, Switzerland
    Structure 11:947-59. 2003
    ....
  13. doi request reprint Mapping the conformational space accessible to BACE2 using surface mutants and cocrystals with Fab fragments, Fynomers and Xaperones
    David W Banner
    pRED Pharma Research and Early Development, Small Molecule Research, Discovery Technologies, F Hoffmann La Roche Ltd, 4070 Basel, Switzerland
    Acta Crystallogr D Biol Crystallogr 69:1124-37. 2013
    ..Here, the different strategies used for raising and selecting BACE2 binders for cocrystallization are described and the crystallization success, crystal quality and the time and resources needed to obtain suitable crystals are compared...
  14. pmc Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport
    Eric J Niesor
    Pharmaceuticals Division, F Hoffmann La Roche Ltd, Basel, Switzerland
    J Lipid Res 51:3443-54. 2010
    ..These data suggest that modulation of CETP activity by dalcetrapib does not inhibit CETP-induced pre-β-HDL formation, which may be required to increase reverse cholesterol transport...
  15. doi request reprint Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase
    Zachary K Sweeney
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 18:4352-4. 2008
    ..Pharmacokinetic studies of 5a in rat and dog demonstrated that this compound has good oral bioavailability in animal species. The crystal structure of a complex between HIV-RT and inhibitor 4c is also described...
  16. doi request reprint Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β
    Bernd Bohrmann
    F Hoffmann La Roche Ltd, pRED, Basel, Switzerland
    J Alzheimers Dis 28:49-69. 2012
    ..These studies demonstrated that gantenerumab preferentially interacts with aggregated Aβ in the brain and lowers amyloid-β by eliciting effector cell-mediated clearance...
  17. doi request reprint Combining biophysical screening and X-ray crystallography for fragment-based drug discovery
    Michael Hennig
    F Hoffmann La Roche Ltd, Basel, Switzerland
    Top Curr Chem 317:115-43. 2012
    ..At Roche we have applied this workflow for a number of targets and the experiences will be outlined in this review...
  18. doi request reprint Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-[[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide] as a clinical candidate
    Lilli Anselm
    F Hoffmann La Roche Ltd, Pharma Research, Basel, Switzerland
    Bioorg Med Chem Lett 20:5313-9. 2010
    ..The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase I clinical study with R1663 has been finalized...
  19. doi request reprint Tyramine fragment binding to BACE-1
    Andreas Kuglstatter
    F Hoffmann La Roche, Pharma Research Basel, Grenzacherstr, 4070 Basel, Switzerland
    Bioorg Med Chem Lett 18:1304-7. 2008
    ..Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads...
  20. ncbi request reprint Open prospective multicenter study of conversion to tacrolimus therapy in renal transplant patients experiencing ciclosporin-related side-effects
    Raimund Margreiter
    Landeskrankenhaus Innsbruck, Transplantation, Anichstr, Innsbruck, Austria
    Transpl Int 18:816-23. 2005
    ..Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus...