David C Swinney

Summary

Publications

  1. doi How were new medicines discovered?
    David C Swinney
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Nat Rev Drug Discov 10:507-19. 2011
  2. pmc Characterization of the elongation complex of dengue virus RNA polymerase: assembly, kinetics of nucleotide incorporation, and fidelity
    Zhinan Jin
    Virology DTA, Roche Palo Alto LLC, Palo Alto, California 94034, USA
    J Biol Chem 286:2067-77. 2011
  3. doi Phenotypic vs. target-based drug discovery for first-in-class medicines
    D C Swinney
    Institute for Rare and Neglected Diseases Drug Discovery, Mountain View, California, USA
    Clin Pharmacol Ther 93:299-301. 2013
  4. ncbi Steady state kinetics of spleen tyrosine kinase investigated by a real time fluorescence assay
    Eva Papp
    Department of Biochemical Pharmacology, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Biochemistry 46:15103-14. 2007
  5. doi Steady-state kinetic characterization of kinase activity and requirements for Mg2+ of interleukin-1 receptor-associated kinase-4
    Mohammad Hekmat-Nejad
    Department of Virology, Roche Palo Alto, LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Biochemistry 49:1495-506. 2010
  6. ncbi Biochemical characterization of the inhibition of the dengue virus RNA polymerase by beta-d-2'-ethynyl-7-deaza-adenosine triphosphate
    Derek R Latour
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA, United States
    Antiviral Res 87:213-22. 2010
  7. ncbi A study of the molecular mechanism of binding kinetics and long residence times of human CCR5 receptor small molecule allosteric ligands
    David C Swinney
    Roche Palo Alto, Palo Alto, CA, USA Institute for Rare and Neglected Diseases Drug Discovery, Mountain View, CA, USA
    Br J Pharmacol 171:3364-75. 2014
  8. doi 3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead
    Michael Soth
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 21:3452-6. 2011
  9. ncbi The role of binding kinetics in therapeutically useful drug action
    David C Swinney
    Roche Palo Alto, CA 94304, USA
    Curr Opin Drug Discov Devel 12:31-9. 2009
  10. doi Essential role of the N-terminal domain in the regulation of RIG-I ATPase activity
    Peter Gee
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    J Biol Chem 283:9488-96. 2008

Collaborators

  • Ronald J Hill
  • Jun Zhang
  • David M Rotstein
  • Jerome Deval
  • Georges Vauquelin
  • Zhinan Jin
  • J Michael Bradshaw
  • Gabrielle Heilek
  • David M Goldstein
  • Andreas Jekle
  • Mohammad Hekmat-Nejad
  • Peter Gee
  • Eva Papp
  • David Shaw
  • Michael Soth
  • Derek R Latour
  • Klaus Klumpp
  • Patricia Tran
  • Hoangdung Ho
  • Simon Lee
  • Jim Barnett
  • Marie Dinh
  • Linghao Niu
  • Hasim Zecic
  • Fujun Li
  • Manjiri Ghate
  • Nidhi Arora
  • Tobias Gabriel
  • Roland Billedeau
  • Martin Stahl
  • Kristen McCaleb
  • Allassan Abubakari
  • Nolan Dewdney
  • Humberto Arzeno
  • Sandra Frauchiger
  • Kieran Durkin
  • Sarah Abbot
  • Brian Wong
  • Man Ling Sung
  • Rebecca Suttman
  • Andreas Kuglstatter
  • Joel Mcintosh
  • Paul Weller
  • Jaehyeon Park
  • Brad Loe
  • Stephen J Lok
  • Seth F Harris
  • Robert Henningsen
  • Ina Lee
  • Jim Li
  • Alan K Kutach
  • Hassan Javanbakht
  • Sandra M Wang
  • Suping Ren
  • Isabel Najera
  • Jirair Gevorkyan
  • Pong Kian Chua
  • Dorit Grunberger
  • Fengrong Zuo
  • Joyce K Y Tse
  • Stan Y Tsing
  • Sandra Wang
  • Kung Ching Chang
  • Stacy Wilson

Detail Information

Publications14

  1. doi How were new medicines discovered?
    David C Swinney
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Nat Rev Drug Discov 10:507-19. 2011
    ..We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development...
  2. pmc Characterization of the elongation complex of dengue virus RNA polymerase: assembly, kinetics of nucleotide incorporation, and fidelity
    Zhinan Jin
    Virology DTA, Roche Palo Alto LLC, Palo Alto, California 94034, USA
    J Biol Chem 286:2067-77. 2011
    ..This work reports the first description of presteady-state kinetics and fidelity for an RNA-dependent RNA polymerase from the Flaviviridae family...
  3. doi Phenotypic vs. target-based drug discovery for first-in-class medicines
    D C Swinney
    Institute for Rare and Neglected Diseases Drug Discovery, Mountain View, California, USA
    Clin Pharmacol Ther 93:299-301. 2013
    ..The rationalization for this success was the unbiased identification of the molecular mechanism of action (MMOA)...
  4. ncbi Steady state kinetics of spleen tyrosine kinase investigated by a real time fluorescence assay
    Eva Papp
    Department of Biochemical Pharmacology, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Biochemistry 46:15103-14. 2007
    ..The findings presented here provide the first kinetic description of the Syk enzyme mechanism...
  5. doi Steady-state kinetic characterization of kinase activity and requirements for Mg2+ of interleukin-1 receptor-associated kinase-4
    Mohammad Hekmat-Nejad
    Department of Virology, Roche Palo Alto, LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Biochemistry 49:1495-506. 2010
    ....
  6. ncbi Biochemical characterization of the inhibition of the dengue virus RNA polymerase by beta-d-2'-ethynyl-7-deaza-adenosine triphosphate
    Derek R Latour
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA, United States
    Antiviral Res 87:213-22. 2010
    ..Overall, beta-d-2'-ethynyl-7-deaza-adenosine provides a promising scaffold for the development of inhibitors of dengue virus polymerase...
  7. ncbi A study of the molecular mechanism of binding kinetics and long residence times of human CCR5 receptor small molecule allosteric ligands
    David C Swinney
    Roche Palo Alto, Palo Alto, CA, USA Institute for Rare and Neglected Diseases Drug Discovery, Mountain View, CA, USA
    Br J Pharmacol 171:3364-75. 2014
    ..A greater understanding of the binding kinetics of small molecule allosteric ligand interactions with CCR5 will lead to a better understanding of the binding process and may help discover new molecules that avoid resistance...
  8. doi 3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead
    Michael Soth
    Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    Bioorg Med Chem Lett 21:3452-6. 2011
    ..Learnings from previous Roche p38-selective inhibitors were applied to a new fragment hit, which was optimized to a potent, exquisitely selective preclinical lead with a good pharmacokinetic profile...
  9. ncbi The role of binding kinetics in therapeutically useful drug action
    David C Swinney
    Roche Palo Alto, CA 94304, USA
    Curr Opin Drug Discov Devel 12:31-9. 2009
    ..The value of binding kinetics to drug discovery will be increased through an improved ability to identify optimal kinetic mechanisms and define kinetic structure activity relationships...
  10. doi Essential role of the N-terminal domain in the regulation of RIG-I ATPase activity
    Peter Gee
    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    J Biol Chem 283:9488-96. 2008
    ....
  11. ncbi Kinetic characterization of human JNK2alpha2 reaction mechanism using substrate competitive inhibitors
    Linghao Niu
    Department of Biochemical Pharmacology, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Biochemistry 46:4775-84. 2007
    ....
  12. ncbi Activation mechanism and steady state kinetics of Bruton's tyrosine kinase
    Marie Dinh
    Department of Biochemical Pharmacology, Roche Palo Alto LLC, CA 94304, USA
    J Biol Chem 282:8768-76. 2007
    ..This investigation of BTK provides the first detailed kinetic characterization of a Tec family kinase...
  13. ncbi The contribution of mechanistic understanding to phenotypic screening for first-in-class medicines
    David C Swinney
    1Institute for Rare and Neglected Diseases Drug Discovery, Mountain View, CA, USA
    J Biomol Screen 18:1186-92. 2013
    ..It is concluded that mechanism takes on different connotations depending on context and perspective and that a target need not always be the exclusive definition of mechanism. ..
  14. ncbi Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and safety
    David C Swinney
    Biochemical Pharmacology, Roche Palo Alto, 3431 Hillview Ave Palo Alto, CA 94304, USA
    Curr Top Med Chem 6:461-78. 2006
    ..This principle appears to be independent of target class and provides insight as to intrinsic biochemical features and approaches required for a maximal therapeutic index...