Alan C Cheng

Summary

Affiliation: Amgen Inc
Country: USA

Publications

  1. ncbi request reprint Structure-based identification of small molecule binding sites using a free energy model
    Ryan G Coleman
    Research Technology Center, Pfizer Global Research and Development, Cambridge, Massachusetts 02139, USA
    J Chem Inf Model 46:2631-7. 2006
  2. ncbi request reprint Structure-based maximal affinity model predicts small-molecule druggability
    Alan C Cheng
    Department of Molecular Informatics, Research Technology Center, Pfizer Global Research and Development, Cambridge, Massachusetts 02139, USA
    Nat Biotechnol 25:71-5. 2007
  3. ncbi request reprint Analysis of kinase inhibitor selectivity using a thermodynamics-based partition index
    Alan C Cheng
    Molecular Structure Department, Amgen Inc, 360 Binney Street, Cambridge, Massachusetts 02142, USA
    J Med Chem 53:4502-10. 2010
  4. doi request reprint Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors
    Emily A Peterson
    Medicinal Chemistry, Amgen Inc, 360 Binney St, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 22:4967-74. 2012
  5. doi request reprint Discovery of a potent, selective, and orally bioavailable pyridinyl-pyrimidine phthalazine aurora kinase inhibitor
    Victor J Cee
    Department of Medicinal Chemistry, Amgen Inc, 360 Binney Street, Cambridge, Massachusetts 02142 and Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320, USA
    J Med Chem 53:6368-77. 2010
  6. doi request reprint Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments
    Brian J Stockman
    Pfizer Global Research and Development, Groton, CT 06340, USA
    Chem Biol Drug Des 73:179-88. 2009
  7. ncbi request reprint Enhanced selectivity profile of pyrazole-urea based DFG-out p38alpha inhibitors
    Hu Liu
    Department of Chemistry, Cambridge South Laboratories, Pfizer Inc, 620 Memorial Drive, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 20:4885-91. 2010
  8. doi request reprint The design, synthesis and potential utility of fluorescence probes that target DFG-out conformation of p38alpha for high throughput screening binding assay
    Haile Tecle
    Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA
    Chem Biol Drug Des 74:547-59. 2009
  9. doi request reprint Discovery of triazine-benzimidazoles as selective inhibitors of mTOR
    Emily A Peterson
    Medicinal Chemistry, Amgen Inc, 360 Binney St, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 21:2064-70. 2011
  10. ncbi request reprint N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR
    Holly L Deak
    Department of Medicinal Chemistry, Amgen Inc, One Kendall Square, Building 1000, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 18:1172-6. 2008

Collaborators

Detail Information

Publications20

  1. ncbi request reprint Structure-based identification of small molecule binding sites using a free energy model
    Ryan G Coleman
    Research Technology Center, Pfizer Global Research and Development, Cambridge, Massachusetts 02139, USA
    J Chem Inf Model 46:2631-7. 2006
    ..Combining the method with a functional residue prediction method called SCA (statistical coupling analysis) results in the prediction of potentially druggable allosteric binding sites on p38alpha kinase...
  2. ncbi request reprint Structure-based maximal affinity model predicts small-molecule druggability
    Alan C Cheng
    Department of Molecular Informatics, Research Technology Center, Pfizer Global Research and Development, Cambridge, Massachusetts 02139, USA
    Nat Biotechnol 25:71-5. 2007
    ..We experimentally test two predictions using high-throughput screening of a diverse compound collection. The collective results highlight the utility of our approach as well as strategies for tackling difficult targets...
  3. ncbi request reprint Analysis of kinase inhibitor selectivity using a thermodynamics-based partition index
    Alan C Cheng
    Molecular Structure Department, Amgen Inc, 360 Binney Street, Cambridge, Massachusetts 02142, USA
    J Med Chem 53:4502-10. 2010
    ..For larger "kinome" panels, the partition index allows assessment of selectivity relative to a kinase or multiple kinases of interest...
  4. doi request reprint Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors
    Emily A Peterson
    Medicinal Chemistry, Amgen Inc, 360 Binney St, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 22:4967-74. 2012
    ....
  5. doi request reprint Discovery of a potent, selective, and orally bioavailable pyridinyl-pyrimidine phthalazine aurora kinase inhibitor
    Victor J Cee
    Department of Medicinal Chemistry, Amgen Inc, 360 Binney Street, Cambridge, Massachusetts 02142 and Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320, USA
    J Med Chem 53:6368-77. 2010
    ....
  6. doi request reprint Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments
    Brian J Stockman
    Pfizer Global Research and Development, Groton, CT 06340, USA
    Chem Biol Drug Des 73:179-88. 2009
    ..Caliper assay data and 19F NMR assay data on the PDK1 Interacting Fragment pocket fragments and structurally related compounds identified them as potential allosteric activators of PDK1 function...
  7. ncbi request reprint Enhanced selectivity profile of pyrazole-urea based DFG-out p38alpha inhibitors
    Hu Liu
    Department of Chemistry, Cambridge South Laboratories, Pfizer Inc, 620 Memorial Drive, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 20:4885-91. 2010
    ....
  8. doi request reprint The design, synthesis and potential utility of fluorescence probes that target DFG-out conformation of p38alpha for high throughput screening binding assay
    Haile Tecle
    Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA
    Chem Biol Drug Des 74:547-59. 2009
    ..In addition, a cascade activity assay was utilized to validate the selective binding of these non-classical kinase inhibitors to the unactive form of the enzyme...
  9. doi request reprint Discovery of triazine-benzimidazoles as selective inhibitors of mTOR
    Emily A Peterson
    Medicinal Chemistry, Amgen Inc, 360 Binney St, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 21:2064-70. 2011
    ..41 μM. Lead compound 42 demonstrated up to 83% inhibition of mTOR substrate phosphorylation in a murine pharmacodynamic model...
  10. ncbi request reprint N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR
    Holly L Deak
    Department of Medicinal Chemistry, Amgen Inc, One Kendall Square, Building 1000, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 18:1172-6. 2008
    ..X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein...
  11. doi request reprint Quinazolin-4-piperidin-4-methyl sulfamide PC-1 inhibitors: alleviating hERG interactions through structure based design
    Snahel D Patel
    Pfizer Global Research and Development, Cambridge Laboratories, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 19:3339-43. 2009
    ....
  12. doi request reprint Structure guided design of a series of sphingosine kinase (SphK) inhibitors
    Darin J Gustin
    Department of Chemistry, Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 23:4608-16. 2013
    ....
  13. doi request reprint Structure- and property-based design of aminooxazoline xanthenes as selective, orally efficacious, and CNS penetrable BACE inhibitors for the treatment of Alzheimer's disease
    Hongbing Huang
    Department of Medicinal Chemistry, Amgen Inc, 360 Binney Street, Cambridge, Massachusetts 02142, United States
    J Med Chem 55:9156-69. 2012
    ..Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound 11a resulted in a significant reduction of CNS Aβ40 in naive rats...
  14. ncbi request reprint Optimal charges in lead progression: a structure-based neuraminidase case study
    Kathryn A Armstrong
    Biological Engineering Division, Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Med Chem 49:2470-7. 2006
    ..Taken together, these results suggest that charge optimization is useful in facilitating generation of compound ideas in lead optimization. Our results also provide insight into design of neuraminidase inhibitors...
  15. ncbi request reprint An intuitive approach to measuring protein surface curvature
    Ryan G Coleman
    Research Technology Center, Pfizer Global Research and Development, Cambridge, Massachusetts 02139, USA
    Proteins 61:1068-74. 2005
    ....
  16. doi request reprint Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase
    Victor J Cee
    Department of Medicinal Chemistry, Amgen Inc, One Kendall Square, Bldg 1000, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 19:424-7. 2009
    ..Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase...
  17. ncbi request reprint Structure of the catalytic domain of human polo-like kinase 1
    Michael Kothe
    Pfizer Global Research and Development, Research Technology Center, 620 Memorial Drive, Cambridge, Massachusetts 02139, USA
    Biochemistry 46:5960-71. 2007
    ....
  18. ncbi request reprint Recognition of nucleic acid bases and base-pairs by hydrogen bonding to amino acid side-chains
    Alan C Cheng
    Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143 0448, USA
    J Mol Biol 327:781-96. 2003
    ....
  19. ncbi request reprint Structural diversity and isomorphism of hydrogen-bonded base interactions in nucleic acids
    Bernhard J Walberer
    Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143 0448, USA
    J Mol Biol 327:767-80. 2003
    ..These studies highlight some of the combinatoric and geometric versatility of base interactions and help provide a framework for analyzing and modeling isomorphic interactions and potentially for designing novel nucleic acid structures...
  20. ncbi request reprint Ab initio interaction energies of hydrogen-bonded amino acid side chain[bond]nucleic acid base interactions
    Alan C Cheng
    Department of Biochemistry and Biophysics and Graduate Group in Biophysics, University of California, San Francisco, California 94143 0448, USA
    J Am Chem Soc 126:434-5. 2004
    ..With these calculated intrinsic affinities, it should be possible to better assess the contributions of bidentate hydrogen-bonding interactions to RNA- and DNA-binding specificity...