John S Sack

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. doi request reprint Structural basis for the high-affinity binding of pyrrolotriazine inhibitors of p38 MAP kinase
    John S Sack
    Department of Macromolecular Crystallography, Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Acta Crystallogr D Biol Crystallogr . 2008
  2. doi request reprint Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases
    Chunjian Liu
    Bristol Myers Squibb Research and Development, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 53:6629-39. 2010
  3. doi request reprint Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38 alpha MAP kinase inhibitors
    Stephen T Wrobleski
    Department of Immunology Chemistry, Bristol Myers Squibb, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:2739-44. 2008
  4. ncbi request reprint N-(cycloalkylamino)acyl-2-aminothiazole inhibitors of cyclin-dependent kinase 2. N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 47:1719-28. 2004
  5. ncbi request reprint 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases: highly potent 2,6-Difluorophenacyl analogues
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, 08543 4000, Princeton, NJ, USA
    Bioorg Med Chem Lett 13:2405-8. 2003
  6. doi request reprint Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors
    David K Williams
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:2998-3002. 2010
  7. doi request reprint Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors
    Jagabandhu Das
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:2652-7. 2008
  8. doi request reprint Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily
    Gretchen M Schroeder
    Bristol Myers Squibb Research and Development, Princeton, New Jersey, 08543 4000, USA
    J Med Chem 52:1251-4. 2009
  9. doi request reprint Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors
    Shuqun Lin
    Department of Immunology Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:5864-8. 2010
  10. ncbi request reprint Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 14:2973-7. 2004

Collaborators

Detail Information

Publications31

  1. doi request reprint Structural basis for the high-affinity binding of pyrrolotriazine inhibitors of p38 MAP kinase
    John S Sack
    Department of Macromolecular Crystallography, Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Acta Crystallogr D Biol Crystallogr . 2008
    ..Addition of an extended benzylmorpholine group forces the DFG loop to flip out of position and allows the ligand to make additional interactions with the protein...
  2. doi request reprint Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases
    Chunjian Liu
    Bristol Myers Squibb Research and Development, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 53:6629-39. 2010
    ..The binding mode of 7k with p38α was confirmed by X-ray crystallographic analysis...
  3. doi request reprint Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38 alpha MAP kinase inhibitors
    Stephen T Wrobleski
    Department of Immunology Chemistry, Bristol Myers Squibb, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:2739-44. 2008
    ..Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38 alpha enzyme...
  4. ncbi request reprint N-(cycloalkylamino)acyl-2-aminothiazole inhibitors of cyclin-dependent kinase 2. N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 47:1719-28. 2004
    ..c./i.p. A2780 human ovarian carcinoma xenograft model...
  5. ncbi request reprint 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases: highly potent 2,6-Difluorophenacyl analogues
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, 08543 4000, Princeton, NJ, USA
    Bioorg Med Chem Lett 13:2405-8. 2003
    ..A solid state structure of 21j, a close di-fluoro analogue, bound to CDK2 shows the inhibitor resides coincident with the ATP purine binding site and forms important H-bonds with Leu83 on the protein backbone...
  6. doi request reprint Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors
    David K Williams
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:2998-3002. 2010
    ..Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model...
  7. doi request reprint Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors
    Jagabandhu Das
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:2652-7. 2008
    ..X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38 alpha is also disclosed...
  8. doi request reprint Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily
    Gretchen M Schroeder
    Bristol Myers Squibb Research and Development, Princeton, New Jersey, 08543 4000, USA
    J Med Chem 52:1251-4. 2009
    ..Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials...
  9. doi request reprint Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors
    Shuqun Lin
    Department of Immunology Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:5864-8. 2010
    ..X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed...
  10. ncbi request reprint Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 14:2973-7. 2004
    ..Elaborated analogues 19 and 23 exhibited anticancer activity in mice against P388 murine leukemia. The solid-state structure of 7 bound to CDK2 shows a similar binding mode to the N-acyl analogues...
  11. doi request reprint Discovery of pyrrolo[2,1-f][1,2,4]triazine C6-ketones as potent, orally active p38α MAP kinase inhibitors
    Alaric J Dyckman
    Bristol Myers Squibb, Research and Development, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 21:4633-7. 2011
    ..Incorporation of aryl and heteroaryl ketones at this position led to potent inhibitors with efficacy in in vivo models of acute and chronic inflammation...
  12. ncbi request reprint 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases
    Raj N Misra
    Bristol Myers Squibb Pharmaceutical Research Institute, PO 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 13:1133-6. 2003
    ..The solid state structure of 3 bound to CDK2 shows 3 resides coincident with the ATP purine binding site and forms important H-bonding interactions with Leu83 on the protein backbone...
  13. doi request reprint The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38alpha MAP kinase inhibitor
    John Hynes
    Bristol Myers Squibb, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:1762-7. 2008
    ..Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38alpha inhibitor that is orally efficacious in rodent models of acute and chronic inflammation...
  14. doi request reprint The identification of novel p38α isoform selective kinase inhibitors having an unprecedented p38α binding mode
    Stephen T Wrobleski
    Department of Immunology Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 23:4120-6. 2013
    ..Based on these findings, a general strategy for the rational design of additional promising p38α isoform selective inhibitors by targeting this novel binding mode is proposed. ..
  15. doi request reprint Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities
    Kyoung Soon Kim
    Department of Oncology Chemistry, Bristol Myers Squibb Pharmaceutical Research and Development, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 51:5330-41. 2008
    ..It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model...
  16. doi request reprint Benzothiazole based inhibitors of p38alpha MAP kinase
    Chunjian Liu
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:1874-9. 2008
    ..The proposed binding mode of this new class of p38alpha inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38alpha enzyme...
  17. doi request reprint 5-amino-pyrazoles as potent and selective p38α inhibitors
    Jagabandhu Das
    Bristol Myers Squibb Research and Development, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:6886-9. 2010
    ..Compound 2j was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38α is also disclosed...
  18. ncbi request reprint Design, synthesis, and anti-inflammatory properties of orally active 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine p38alpha mitogen-activated protein kinase inhibitors
    John Hynes
    Department of Immunology Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000, USA
    J Med Chem 51:4-16. 2008
    ..In rodent disease models of chronic inflammation, multiple compounds demonstrated significant inhibition of disease progression leading to the advancement of 2 compounds 11b and 11j into further preclinical and toxicological studies...
  19. doi request reprint N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation
    Alexandra A Nirschl
    Discovery Chemistry, Analytical Research and Development, Bristol Myers Squibb Research and Development, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 52:2794-8. 2009
    ..Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model...
  20. ncbi request reprint Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold
    Chongqing Sun
    Bristol Myers Squibb Pharmaceutical Research Institute, Post Office Box 5400, Princeton, NJ 08543 5400, USA
    J Med Chem 49:7596-9. 2006
    ..After oral dosing in a rat atrophied levator ani muscle model, (7R,7aS)-10b demonstrated efficacy at restoring levator ani muscle mass to that of intact controls and exhibited >50-fold selectivity for muscle over prostate...
  21. doi request reprint X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family kinase
    Jodi Muckelbauer
    Chemical and Protein Technologies, Bristol Myers Squibb, PO Box 4000, Princeton, NJ 08543, USA
    Chem Biol Drug Des 78:739-48. 2011
    ..The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors...
  22. ncbi request reprint Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta
    Jon J Hangeland
    Pharmaceutical Research Institute, Bristol Myers Squibb, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 14:3549-53. 2004
    ..Movement of this amino acid side chain provides an expanded pocket for the bulky side chain while the ligand-receptor complex retains full agonist activity...
  23. doi request reprint Pyrrolo[1,2-f]triazines as JAK2 inhibitors: achieving potency and selectivity for JAK2 over JAK3
    Lalgudi S Harikrishnan
    Bristol Myers Squibb Co, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 21:1425-8. 2011
    ..SAR studies of pyrrolo[1,2-f]triazines as JAK2 inhibitors is presented. Achieving JAK2 inhibition selectively over JAK3 is discussed...
  24. doi request reprint Structural basis for CARM1 inhibition by indole and pyrazole inhibitors
    John S Sack
    Bristol Myers Squibb Research and Development, P O Box 4000, Princeton, NJ 08543 4000, USA
    Biochem J 436:331-9. 2011
    ..Together, the structural and biophysical information should aid in the design of both potent and specific inhibitors of CARM1...
  25. ncbi request reprint Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X-ray crystallographic analysis, and biological activities
    Kyoung Soon Kim
    Department of Oncology Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000, USA
    J Med Chem 45:3905-27. 2002
    ....
  26. ncbi request reprint Synthesis and SAR of p38alpha MAP kinase inhibitors based on heterobicyclic scaffolds
    T G Murali Dhar
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 17:5019-24. 2007
    ..X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38alpha is also disclosed...
  27. doi request reprint Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:3224-9. 2008
    ..These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model...
  28. ncbi request reprint Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)
    Upender Velaparthi
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 17:2317-21. 2007
    ..Installing amine containing side chains at the 4-position of pyridone ring significantly improved the enzyme potency. SAR and biological activity of these compounds is presented...
  29. ncbi request reprint Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats
    Jacek Ostrowski
    Department of Metabolic Diseases, Bristol Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543, USA
    Endocrinology 148:4-12. 2007
    ....
  30. doi request reprint Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase
    Anthony J Sampognaro
    Department of Discovery Chemistry, Bristol Myers Squibb Research and Development, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 20:5027-30. 2010
    ....
  31. ncbi request reprint Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664
    Jagabandhu Das
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 12:45-9. 2002
    ....