Michael D Shultz

Summary

Affiliation: Novartis Institutes for BioMedical Research

Publications

  1. doi request reprint Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts 02139, United States
    J Med Chem 54:4752-72. 2011
  2. doi request reprint [1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazoles: antagonists of the Wnt pathway that inhibit tankyrases 1 and 2 via novel adenosine pocket binding
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts 02319, United States
    J Med Chem 55:1127-36. 2012
  3. doi request reprint Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
    J Med Chem 56:6495-511. 2013
  4. doi request reprint Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA Electronic address
    Bioorg Med Chem Lett 23:5980-91. 2013
  5. doi request reprint The thermodynamic basis for the use of lipophilic efficiency (LipE) in enthalpic optimizations
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA Electronic address
    Bioorg Med Chem Lett 23:5992-6000. 2013
  6. doi request reprint The design, synthesis and structure-activity relationships of novel isoindoline-based histone deacetylase inhibitors
    Michael Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 21:4909-12. 2011
  7. doi request reprint Structure-efficiency relationship of [1,2,4]triazol-3-ylamines as novel nicotinamide isosteres that inhibit tankyrases
    Michael D Shultz
    Novartis Institutes for Biomedical Research Incorporated, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
    J Med Chem 56:7049-59. 2013
  8. pmc Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939
    Christina A Kirby
    Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 68:115-8. 2012

Detail Information

Publications8

  1. doi request reprint Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts 02139, United States
    J Med Chem 54:4752-72. 2011
    ..Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels...
  2. doi request reprint [1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazoles: antagonists of the Wnt pathway that inhibit tankyrases 1 and 2 via novel adenosine pocket binding
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts 02319, United States
    J Med Chem 55:1127-36. 2012
    ..Furthermore, a cocrystal structure of compound 24 complexed to TNKS1 demonstrates an alternate binding mode for PARP family member proteins that does not involve interactions with the nicotinamide binding pocket...
  3. doi request reprint Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
    J Med Chem 56:6495-511. 2013
    ....
  4. doi request reprint Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA Electronic address
    Bioorg Med Chem Lett 23:5980-91. 2013
    ....
  5. doi request reprint The thermodynamic basis for the use of lipophilic efficiency (LipE) in enthalpic optimizations
    Michael D Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA Electronic address
    Bioorg Med Chem Lett 23:5992-6000. 2013
    ..The basis for the prioritization of LipE over other metrics in enthalpic optimizations is described. ..
  6. doi request reprint The design, synthesis and structure-activity relationships of novel isoindoline-based histone deacetylase inhibitors
    Michael Shultz
    Novartis Institutes for BioMedical Research, Inc, 250 Massachusetts Avenue, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 21:4909-12. 2011
    ..The in vitro safety profiles of selected compounds were assessed and shown to be suitable for further lead optimization...
  7. doi request reprint Structure-efficiency relationship of [1,2,4]triazol-3-ylamines as novel nicotinamide isosteres that inhibit tankyrases
    Michael D Shultz
    Novartis Institutes for Biomedical Research Incorporated, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
    J Med Chem 56:7049-59. 2013
    ..These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization. ..
  8. pmc Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939
    Christina A Kirby
    Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 68:115-8. 2012
    ..The TNKS1-PJ34 crystallization system was used to determine the structure of TNKS1 in complex with XAV939. These structures provide a basis for the start of a structure-based drug-design campaign for TNKS1...