Philip Jones

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. doi A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 51:2350-3. 2008
  2. doi Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors
    Danila Branca
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600 Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 19:4042-5. 2009
  3. doi Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors
    Philip Jones
    IRBM Merck Research Labs Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 52:7170-85. 2009
  4. ncbi From natural products to small molecule ketone histone deacetylase inhibitors: development of new class specific agents
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Curr Pharm Des 14:545-61. 2008
  5. ncbi A series of novel, potent, and selective histone deacetylase inhibitors
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 16:5948-52. 2006
  6. ncbi 2-Trifluoroacetylthiophenes, a novel series of potent and selective class II histone deacetylase inhibitors
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 18:3456-61. 2008
  7. doi Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 18:1814-9. 2008
  8. ncbi Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy
    Jesus M Ontoria
    Istituto di Ricerche di Biologia Molecolare, P Angeletti SpA IRBM MRL, Rome, Via Pontina Km 30, 600, I 00040 Pomezia, Italy
    J Med Chem 52:6782-9. 2009
  9. ncbi Optimization of a series of potent and selective ketone histone deacetylase inhibitors
    Giovanna Pescatore
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 18:5528-32. 2008
  10. doi Identification of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors
    Federica Orvieto
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 19:4196-200. 2009

Collaborators

Detail Information

Publications29

  1. doi A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 51:2350-3. 2008
    ..A representative example has demonstrated tumor growth inhibition in a human colon HCT-116 carcinoma xenograft model comparable to known inhibitors...
  2. doi Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors
    Danila Branca
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600 Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 19:4042-5. 2009
    ..SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay...
  3. doi Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors
    Philip Jones
    IRBM Merck Research Labs Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 52:7170-85. 2009
    ..Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer...
  4. ncbi From natural products to small molecule ketone histone deacetylase inhibitors: development of new class specific agents
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Curr Pharm Des 14:545-61. 2008
    ....
  5. ncbi A series of novel, potent, and selective histone deacetylase inhibitors
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 16:5948-52. 2006
    ..SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates...
  6. ncbi 2-Trifluoroacetylthiophenes, a novel series of potent and selective class II histone deacetylase inhibitors
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 18:3456-61. 2008
    ..X-ray crystal structures of the HDAC 4 catalytic domain with a bound inhibitor demonstrate these compounds are active site inhibitors and bind in their hydrated form...
  7. doi Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases
    Philip Jones
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 18:1814-9. 2008
    ..The low efficiency can be restored either by: mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate, allowing the development of assays to identify class IIa HDAC inhibitors...
  8. ncbi Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy
    Jesus M Ontoria
    Istituto di Ricerche di Biologia Molecolare, P Angeletti SpA IRBM MRL, Rome, Via Pontina Km 30, 600, I 00040 Pomezia, Italy
    J Med Chem 52:6782-9. 2009
    ..Compounds 6h and 2 show inhibition of alpha-tubulin deacetylation in HCT116 cells at 1 microM concentration and antiproliferation effects only at concentrations where inhibition of histone H3 deacetylation is observed...
  9. ncbi Optimization of a series of potent and selective ketone histone deacetylase inhibitors
    Giovanna Pescatore
    IRBM Merck Research Laboratories, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 18:5528-32. 2008
    ..Herein we describe the optimization of a series of ketone small molecule HDAC inhibitors leading to potent and selective class I HDAC inhibitors with good dog PK...
  10. doi Identification of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors
    Federica Orvieto
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 19:4196-200. 2009
    ..An extensive SAR around the 3-position of pyrazole in the scaffold led to the discovery of amides derivatives as low nanomolar PARP-1 inhibitors...
  11. doi 2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors
    Ester Muraglia
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600 Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 18:6083-7. 2008
    ....
  12. doi Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties
    Olaf Kinzel
    IRBM Merck Research Laboratories, Pomezia, Italy
    J Med Chem 52:3453-6. 2009
    ..In a mouse xenograft model it shows efficacy comparable to that of vorinostat at a 10-fold reduced dose...
  13. doi Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors
    Rita Scarpelli
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia 00040, Rome, Italy
    Bioorg Med Chem Lett 18:6078-82. 2008
    ..A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors...
  14. doi Synthesis and biological evaluation of substituted 2-phenyl-2H-indazole-7-carboxamides as potent poly(ADP-ribose) polymerase (PARP) inhibitors
    Rita Scarpelli
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia 00040, Rome, Italy
    Bioorg Med Chem Lett 20:488-92. 2010
    ....
  15. doi Identification and SAR of novel pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)
    Giovanna Pescatore
    IRBM Merck Research Laboratories, 00040 Pomezia, Italy
    Bioorg Med Chem Lett 20:1094-9. 2010
    ..Optimization led to compounds that display excellent PARP-1 enzyme potency and inhibit the proliferation of BRCA deficient cells in the low double-digit nanomolar range showing excellent selectivity over BRCA proficient cancer cells...
  16. doi Histone deacetylase inhibitors with a primary amide zinc binding group display antitumor activity in xenograft model
    Barbara Attenni
    IRBM Merck Research Laboratories, Pomezia, Rome, Italy
    Bioorg Med Chem Lett 19:3081-4. 2009
    ..This HDACi displays good antiproliferative activity against multiple cancer cell lines, and demonstrates efficacy in a xenograft model comparable to vorinostat...
  17. doi Discovery of N-[(1-aryl-1H-indazol-5-yl)methyl]amides derivatives as smoothened antagonists for inhibition of the hedgehog pathway
    Gabriella Dessole
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia 00040, Rome, Italy
    Bioorg Med Chem Lett 19:4191-5. 2009
    ..Identification of the lead structure 1 by HTS, followed by SAR study on the amide and aryl portions led to the discovery of antagonists with nanomolar activity...
  18. doi Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors
    Jesus M Ontoria
    IRBM, Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 21:5274-82. 2011
    ..These compounds are valuable tools with which to probe the biology of the Hh-pathway...
  19. doi Discovery and SAR of novel, potent and selective hexahydrobenzonaphthyridinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)
    Caterina Torrisi
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 20:448-52. 2010
    ....
  20. doi N-(2-alkylaminoethyl)-4-(1,2,4-oxadiazol-5-yl)piperazine-1-carboxamides as highly potent smoothened antagonists
    Ester Muraglia
    IRBM, Merck Research Laboratories Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 21:5283-8. 2011
    ....
  21. pmc Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex
    Alessandro Vannini
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Via Pontina Km 30 600, 00040 Pomezia, Rome, Italy
    EMBO Rep 8:879-84. 2007
    ..The crucial role of Asp 101 in substrate and inhibitor recognition was confirmed by activity and binding assays of wild-type HDAC8 and Asp101Ala, Tyr306Phe and Asp101Ala/Tyr306Phe mutants...
  22. doi N-(4-Fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamides a novel class of potent HIV-1 integrase inhibitors
    Alessia Petrocchi
    Departments of Medicinal Chemistry and Drug Metabolism IRBM MRL, Via Pontina, Km 30 600, 00040 Pomezia RM, Italy
    Bioorg Med Chem Lett 19:4245-9. 2009
    ....
  23. doi PISA, a novel pharmacodynamic assay for assessing poly(ADP-ribose) polymerase (PARP) activity in situ
    Laura S Lubbers
    Department of Stroke and Neurodegeneration, Merck Research Laboratories, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486, USA
    J Pharmacol Toxicol Methods 61:319-28. 2010
    ..We developed the PARP In Situ Activity (PISA) assay to provide a direct, quantitative assessment of CNS PARP activity in vitro or in vivo...
  24. doi Smoothened antagonists: a promising new class of antitumor agents
    Paola Gallinari
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Department of Oncology, IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy 39 06 91093232 39 06 91093549
    Expert Opin Drug Discov 4:525-44. 2009
    ..3) Our knowledge of the biology of hedgehog signaling in cancer is still very incomplete and significant efforts will be required to understand how to use the emerging novel agents in the clinic...
  25. doi Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection
    Vincenzo Summa
    Istituto di Ricerche di Biologia Molecolare, P Angeletti SpA Merck Research Laboratories, Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 51:5843-55. 2008
    ....
  26. pmc Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain
    Matthew J Bottomley
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Merck Research Laboratories, Via Pontina Km 30 600, 00040 Pomezia Roma, Italy
    J Biol Chem 283:26694-704. 2008
    ..HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions...
  27. ncbi Pharmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a functionally selective GABA(A) alpha5 inverse agonist for cognitive dysfunction
    Philip Jones
    Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    Bioorg Med Chem Lett 16:872-5. 2006
    ..An unusual oxidation of the pyrazolo[1,5-d][1,2,4]triazine core to the corresponding pyrazolo[1,5-d][1,2,4]triazin-4(5H)-one scaffold by aldehyde oxidase has been observed...
  28. ncbi Helicobacter pylori: antibiotic resistance and eradication rates in Suffolk, UK, 1991-2001
    Ewen A B Cameron
    Department of Gastroenterology and Public Health Laboratory Service, Ipswich Hospital, Heath Road, Ipswich IP4 5PD, UK
    J Med Microbiol 53:535-8. 2004
    ..001). Whilst metronidazole resistance is increasing in Suffolk, this does not seem to have a significant effect on eradication rates. Metronidazole-based regimes are still effective first-line treatments in most patients...
  29. pmc Effects of infection with transmissible gastroenteritis virus on concomitant immune responses to dietary and injected antigens
    Michael Bailey
    Department of Clinical Veterinary Science, University of Bristol, Bristol BS40 5DU, United Kingdom
    Clin Diagn Lab Immunol 11:337-43. 2004
    ....