P M Blumberg

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Function of RasGRP3 in the formation and progression of human breast cancer
    Zsuzsanna Nagy
    DE MTA Lendület Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Nagyerdei krt, 98, PO Box 22, Debrecen H 4032, Hungary
    Mol Cancer 13:96. 2014
  2. doi request reprint Lighting a backfire to quench the blaze: a combined drug approach targeting the vanilloid receptor TRPV1
    Peter M Blumberg
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Interv 7:310-2. 2007
  3. ncbi request reprint Evodiamine functions as an agonist for the vanilloid receptor TRPV1
    Larry V Pearce
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892 4255, USA
    Org Biomol Chem 2:2281-6. 2004
  4. pmc TRPV1 activation is not an all-or-none event: TRPV1 partial agonism/antagonism and its regulatory modulation
    Peter M Blumberg
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 4255, USA
    Curr Top Med Chem 11:2151-8. 2011
  5. pmc Wealth of opportunity - the C1 domain as a target for drug development
    P M Blumberg
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Center, Bethesda, MD 20892, USA
    Curr Drug Targets 9:641-52. 2008
  6. ncbi request reprint An optimized protein kinase C activating diacylglycerol combining high binding affinity (Ki) with reduced lipophilicity (log P)
    K Nacro
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
    J Med Chem 44:1892-904. 2001
  7. ncbi request reprint Overexpression of protein kinase C-delta and -epsilon in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity
    H Mischak
    Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892
    J Biol Chem 268:6090-6. 1993
  8. ncbi request reprint Phorbol ester-induced myeloid differentiation is mediated by protein kinase C-alpha and -delta and not by protein kinase C-beta II, -epsilon, -zeta, and -eta
    H Mischak
    Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892 0037
    J Biol Chem 268:20110-5. 1993
  9. ncbi request reprint Comparison of the roles of the C1a and C1b domains of protein kinase C alpha in ligand induced translocation in NIH 3T3 cells
    K Bogi
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892 4255, USA
    FEBS Lett 456:27-30. 1999
  10. ncbi request reprint The cloned rat vanilloid receptor VR1 mediates both R-type binding and C-type calcium response in dorsal root ganglion neurons
    A Szallasi
    National Cancer Institute, Bethesda, Maryland, USA
    Mol Pharmacol 56:581-7. 1999

Collaborators

Detail Information

Publications100

  1. pmc Function of RasGRP3 in the formation and progression of human breast cancer
    Zsuzsanna Nagy
    DE MTA Lendület Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Nagyerdei krt, 98, PO Box 22, Debrecen H 4032, Hungary
    Mol Cancer 13:96. 2014
    ..Here, we investigated the putative alteration of expression and potential function of RasGRP3 in the formation and progression of human breast cancer...
  2. doi request reprint Lighting a backfire to quench the blaze: a combined drug approach targeting the vanilloid receptor TRPV1
    Peter M Blumberg
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Interv 7:310-2. 2007
    ....
  3. ncbi request reprint Evodiamine functions as an agonist for the vanilloid receptor TRPV1
    Larry V Pearce
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892 4255, USA
    Org Biomol Chem 2:2281-6. 2004
    ..We conclude that evodiamine represents a novel class of agonists for rat TRPV1, albeit 3-19-fold less potent than capsaicin, and thus represents a new potential class of lead molecules for drug development...
  4. pmc TRPV1 activation is not an all-or-none event: TRPV1 partial agonism/antagonism and its regulatory modulation
    Peter M Blumberg
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 4255, USA
    Curr Top Med Chem 11:2151-8. 2011
    ..Partial agonism/partial antagonism, its modulation by signaling pathways, variable desensitization, and slow kinetics of action can all be exploited through drug design...
  5. pmc Wealth of opportunity - the C1 domain as a target for drug development
    P M Blumberg
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Center, Bethesda, MD 20892, USA
    Curr Drug Targets 9:641-52. 2008
    ..Finally, the complexity of the factors contributing to ligand - C1 domain interactions affords abundant opportunities for manipulation of selectivity; indeed, substantially selective compounds have already been identified...
  6. ncbi request reprint An optimized protein kinase C activating diacylglycerol combining high binding affinity (Ki) with reduced lipophilicity (log P)
    K Nacro
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
    J Med Chem 44:1892-904. 2001
    ..The DAG analogue of 3B in which the acyl groups are reversed (2C) showed a decrease in binding affinity reflecting the capacity of PK-C to effectively discriminate between alternative orientations of the acyl chains...
  7. ncbi request reprint Overexpression of protein kinase C-delta and -epsilon in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity
    H Mischak
    Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892
    J Biol Chem 268:6090-6. 1993
    ..NIH 3T3 cells that overexpress PKC-epsilon also form tumors in nude mice with 100% incidence. This indicates that high expression of PKC-epsilon contributes to neoplastic transformation...
  8. ncbi request reprint Phorbol ester-induced myeloid differentiation is mediated by protein kinase C-alpha and -delta and not by protein kinase C-beta II, -epsilon, -zeta, and -eta
    H Mischak
    Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892 0037
    J Biol Chem 268:20110-5. 1993
    ..These results indicate that only these two members of the PKC gene family can participate in TPA-induced myeloid differentiation...
  9. ncbi request reprint Comparison of the roles of the C1a and C1b domains of protein kinase C alpha in ligand induced translocation in NIH 3T3 cells
    K Bogi
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892 4255, USA
    FEBS Lett 456:27-30. 1999
    ..These results contrast with those previously reported for PKC delta, suggesting that the domains play different roles in different PKC isoforms...
  10. ncbi request reprint The cloned rat vanilloid receptor VR1 mediates both R-type binding and C-type calcium response in dorsal root ganglion neurons
    A Szallasi
    National Cancer Institute, Bethesda, Maryland, USA
    Mol Pharmacol 56:581-7. 1999
    ..We conclude that VR1 can account for both the ligand binding and calcium uptake observed in rat DRG neurons...
  11. ncbi request reprint Analysis of the native quaternary structure of vanilloid receptor 1
    N Kedei
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:28613-9. 2001
    ..Finally, differences in glycosylation between the systems were observed, indicating the need for caution in the use of the heterologous expression systems for analysis of VR1 properties...
  12. ncbi request reprint Role of hydrophobic residues in the C1b domain of protein kinase C delta on ligand and phospholipid interactions
    Q J Wang
    Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion and Laboratory of Medicinal Chemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:19580-7. 2001
    ..More generally, the results emphasize the interplay between the C1 domain, ligand, and phospholipid in the ternary binding complex...
  13. pmc Resiniferatoxin-type phorboid vanilloids display capsaicin-like selectivity at native vanilloid receptors on rat DRG neurons and at the cloned vanilloid receptor VR1
    A Szallasi
    National Cancer Institute, Bethesda, Maryland, USA
    Br J Pharmacol 128:428-34. 1999
    ..Furthermore, PDDHV now provides a tool to explore the biological correlates of capsaicin-type vanilloid pharmacology...
  14. ncbi request reprint The catalytic domain of PKC-epsilon, in reciprocal PKC-delta and -epsilon chimeras, is responsible for conferring tumorgenicity to NIH3T3 cells, whereas both regulatory and catalytic domains of PKC-epsilon contribute to in vitro transformation
    Q J Wang
    Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    Oncogene 16:53-60. 1998
    ....
  15. ncbi request reprint Differential role of specific PKC isoforms in the proliferation of glial cells and the expression of the astrocytic markers GFAP and glutamine synthetase
    C Brodie
    Molecular Mechanisms of Tumor Promotion Section, LCCTP, NCI, NIH, Bethesda, MD 20892, USA
    Brain Res Mol Brain Res 56:108-17. 1998
    ....
  16. ncbi request reprint Protein kinase C. Modeling of the binding site and prediction of binding constants
    S Wang
    Laboratory of Medicinal Chemistry, DCT, National Cancer Institute, NIH, Bethesda, Maryland 20892
    J Med Chem 37:1326-38. 1994
    ....
  17. ncbi request reprint Phorbol esters modulate the Ras exchange factor RasGRP3
    P S Lorenzo
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    Cancer Res 61:943-9. 2001
    ..We conclude that RasGRP3 serves as a PKC-independent pathway to link the tumor-promoting phorbol esters with activation of Ras GTPases...
  18. ncbi request reprint Regulation of actin cytoskeleton in lymphocytes: PKC-delta disrupts IL-3-induced membrane ruffles downstream of Rac1
    L Y Romanova
    Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    J Cell Physiol 179:157-69. 1999
    ..Experiments with overexpression in Baf3 of individual PKC isoforms and a dominant negative PKC-delta indicate that activation of PKC-delta but not other PKC isoforms is responsible for disruption of membrane ruffles...
  19. pmc RasGRP3, a Ras activator, contributes to signaling and the tumorigenic phenotype in human melanoma
    D Yang
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 4255, USA
    Oncogene 30:4590-600. 2011
    ..The identification of the role of RasGRP3 in melanoma highlights its importance, as a Ras activator, in the phosphoinositide signaling pathway in human melanoma and provides a new potential therapeutic target...
  20. ncbi request reprint Tyrosine phosphorylation-dependent and -independent associations of protein kinase C-delta with Src family kinases in the RBL-2H3 mast cell line: regulation of Src family kinase activity by protein kinase C-delta
    J S Song
    Section on Chemical Immunology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
    Oncogene 16:3357-68. 1998
    ..Thus, the interaction and cross-talk of PKC-delta with Src family kinases suggests a novel and inter-dependent mechanism for regulation of enzymatic activity that may serve an important role in cellular responses...
  21. pmc Comparison of transcriptional response to phorbol ester, bryostatin 1, and bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into their differential mechanism of action
    N Kedei
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Biochem Pharmacol 85:313-24. 2013
    ....
  22. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 24. Asymmetric synthesis of a chiral (R)-DAG-lactone template as a versatile precursor for highly functionalized DAG-lactones
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    Org Lett 6:2413-6. 2004
    ..The synthesis of the most potent DAG-lactones known to date, (Z)-10 and (E)-10, served to confirm PK-C's exclusive preference for the (R)-stereochemistry in this class of compounds...
  23. ncbi request reprint Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1
    Z Olah
    Neuronal Gene Expression Unit, Pain and Neurosensory Mechanisms Branch, NIDCR, the Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:11021-30. 2001
    ..These data demonstrate that vanilloids disrupt vital organelles within the cell body and, if administered to sensory ganglia, may be employed to rapidly and selectively delete nociceptive neurons...
  24. pmc A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors
    A Szallasi
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri, USA
    Br J Pharmacol 126:1351-8. 1999
    ..6. In conclusion, scutigeral and its congeners form a new chemical class of vanilloids, the triprenyl phenols. Scutigeral promises to be a novel chemical lead for the development of orally active, non-pungent vanilloids...
  25. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). 27. Modulation of membrane translocation of protein kinase C (PKC) isozymes alpha and delta by diacylglycerol lactones (DAG-lactones) containing rigid-rod acyl groups
    Krishnan Malolanarasimhan
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 50:962-78. 2007
    ....
  26. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 26. Exploring the chemical space surrounding the C1 domain of protein kinase C with DAG-lactones containing aryl groups at the sn-1 and sn-2 positions
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 49:3185-203. 2006
    ..We conclude that DAG-lactones containing alpha-phenylalkylidene side chains at the sn-2 position represent excellent scaffolds upon which to explore further chemical diversity...
  27. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 19. Synthesis and protein kinase C binding affinity of diacylglycerol lactones bearing an N-hydroxylamide side chain
    Yongseok Choi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 46:2790-3. 2003
    ..Here, we report the synthesis and complete characterization of 1a and 1b together with the associated biological activity in terms of PK-C binding affinity...
  28. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). 23. Hydrophobic ligand-protein interactions versus ligand-lipid interactions of DAG-lactones with protein kinase C (PK-C)
    Hirokazu Tamamura
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Building 376, Room 104, Frederick, Maryland 21702, USA
    J Med Chem 47:4858-64. 2004
    ....
  29. pmc Rational design of drugs that induce human immunodeficiency virus replication
    Dean H Hamer
    Laboratory of Biochemistry, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Virol 77:10227-36. 2003
    ..These studies demonstrate the potential for the rational design of agents that, in conjunction with HAART and HIV-specific toxins, can be used to decrease or eliminate the pool of latently infected reservoirs by forcing viral expression...
  30. ncbi request reprint Arachidonyl dopamine as a ligand for the vanilloid receptor VR1 of the rat
    Attila Toth
    Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bldg 37, Rm 4048, 37 Convent Dr, MSC 4255, Bethesda, MD 20892 4255, USA
    Life Sci 73:487-98. 2003
    ..We conclude that AA-DO is a full agonist for VR1 with a potency in the low micromolar range and is able to significantly desensitize the cells in a time and dose dependent manner...
  31. ncbi request reprint Differential activation and desensitization of sensory neurons by resiniferatoxin
    G Acs
    Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Neurosci 17:5622-8. 1997
    ..Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization...
  32. pmc Taxonomy and function of C1 protein kinase C homology domains
    J H Hurley
    Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0580, USA
    Protein Sci 6:477-80. 1997
    ..Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not...
  33. ncbi request reprint The catalytic domain of protein kinase C-delta in reciprocal delta and epsilon chimeras mediates phorbol ester-induced macrophage differentiation of mouse promyelocytes
    Q J Wang
    Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    J Biol Chem 272:76-82. 1997
    ..These results demonstrate that the catalytic domain of PKC-delta contains the primary determinants for its activity in phorbol ester-induced macrophage differentiation...
  34. ncbi request reprint Differential binding modes of diacylglycerol (DAG) and DAG lactones to protein kinase C (PK-C)
    Dina M Sigano
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 46:1571-9. 2003
    ..As these analogous DAGs and DAG lactones have almost identical log P values, this difference in binding affinity is a direct result of the entropic advantage of constraining the glycerol backbone...
  35. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 20. The search for an elusive binding site on protein kinase C through relocation of the carbonyl pharmacophore along the sn-1 side chain of 1,2-diacylglycerol lactones
    Hirokazu Tamamura
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 47:644-55. 2004
    ..A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface...
  36. ncbi request reprint Design of a high-affinity competitive antagonist of the vanilloid receptor selective for the calcium entry-linked receptor population
    Attila Toth
    Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    Mol Pharmacol 65:282-91. 2004
    ..In summary, IBTU is a novel, potent TRPV1 antagonist with marked selectivity between subpopulations of TRPV1 and may permit the function of these distinct pools to be explored and potentially exploited...
  37. ncbi request reprint Characterization of the interaction of ingenol 3-angelate with protein kinase C
    Noemi Kedei
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    Cancer Res 64:3243-55. 2004
    ..The in vitro kinase activity of PKC-alpha induced by I3A was lower than that induced by PMA. The novel pattern of behavior of I3A makes it of great interest for further evaluation...
  38. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 21. A solid-phase method of synthesis of diacylglycerol lactones as a prelude to a combinatorial approach for the synthesis of protein kinase C isozyme-specific ligands
    Dehui Duan
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA
    J Med Chem 47:3248-54. 2004
    ..The biological results obtained using the crude samples directly obtained from the resin compared well with those from pure materials, as the K(i) values between the two sets varied only by a factor between 1.5 and 3.7...
  39. ncbi request reprint Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1
    Attila Toth
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bldg 37, Room 4048, 37 Convent Dr, MSC 4255, Bethesda, MD 20892 4255, United States
    Life Sci 76:2921-32. 2005
    ..We conclude that structurally diverse vanilloid agonists induce marked diversity in the patterns of Ca2+ response. This diversity of response may provide opportunities for pharmacological exploitation...
  40. pmc Conformationally constrained analogues of diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 carbonyl functionality reveals the essential role of the sn-1 carbonyl at the lipid interface in the binding of DAG-lactones to protein kinase C
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 48:5738-48. 2005
    ..The parent DAG-lactones, E-6 and Z-7, were designed to bind exclusively in the sn-2 binding mode to ensure the correct orientation and disposition of pharmacophores at the binding site...
  41. pmc Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths
    Maria J Comin
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Med Chem 52:3274-83. 2009
    ..The different spatial disposition of the rigid structural motif on the DAG-lactones contributes to differential activity...
  42. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). 28. DAG-dioxolanones reveal a new additional interaction site in the C1b domain of PKC delta
    Yongseok Choi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 50:3465-81. 2007
    ..Using this approach, we show that the C1b domain of PKC delta plays the predominant role in the translocation of PKC delta to the membrane in the presence of DAG...
  43. ncbi request reprint Activation of latent HIV-1 expression by the potent anti-tumor promoter 12-deoxyphorbol 13-phenylacetate
    Sven Bocklandt
    National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Antiviral Res 59:89-98. 2003
    ..The combination of high potency and anti-tumor promoting activity make DPP an attractive candidate for the adjunctive therapy of persistent HIV-1 infection...
  44. ncbi request reprint High affinity antagonists of the vanilloid receptor
    Yun Wang
    National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Pharmacol 62:947-56. 2002
    ..We conclude that JYL1421 is a competitive antagonist of rVR1, blocking response to all three of the agonists (capsaicin, heat, and protons) with enhanced potency relative to capsazepine...
  45. ncbi request reprint Thapsigargin binds to and inhibits the cloned vanilloid receptor-1
    Attila Toth
    Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Building 37, Room 3A01, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA
    Biochem Biophys Res Commun 293:777-82. 2002
    ..We conclude that thapsigargin represents a new prototype of a VR1 inhibitor and that caution should be exercised in interpreting the effects of thapsigargin, especially when it is used in the micromolar range to inhibit SERCA activity...
  46. ncbi request reprint Cholesterol sulfate activates multiple protein kinase C isoenzymes and induces granular cell differentiation in cultured murine keratinocytes
    M F Denning
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cell Growth Differ 6:1619-26. 1995
    ....
  47. ncbi request reprint Development of a rapid approach to identification of tyrosine phosphorylation sites: application to PKC delta phosphorylated upon activation of the high affinity receptor for IgE in rat basophilic leukemia cells
    Z Szallasi
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA
    Biochem Biophys Res Commun 214:888-94. 1995
    ..Single mutants in each of these three tyrosine residues of PKC delta were prepared. Upon expression in the RBL-2H3 cells, only the mutant in tryosine 52 showed abolition of the IgE-antigen induced tyrosine phosphorylation...
  48. ncbi request reprint High-affinity partial agonists of the vanilloid receptor
    Yun Wang
    National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892 4255, USA
    Mol Pharmacol 64:325-33. 2003
    ..Our results emphasize, moreover, the strong dependence of such partial agonists on other modulators of rVR1 and predict that their biological behavior will depend strongly on biological context...
  49. pmc Conformationally constrained analogues of diacylglycerol. 30. An investigation of diacylglycerol-lactones containing heteroaryl groups reveals compounds with high selectivity for Ras guanyl nucleotide-releasing proteins
    Said El Kazzouli
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Med Chem 51:5371-86. 2008
    ..The results clearly show that the combination of chemical and physical properties in these molecules needs to be perfectly balanced to achieve the desired specificity...
  50. pmc Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors
    Larry V Pearce
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Naunyn Schmiedebergs Arch Pharmacol 377:149-57. 2008
    ..A further implication is that it may be desirable to tailor screening approaches for drug discovery to reflect the desired regulatory state of the targeted TRPV1...
  51. ncbi request reprint Interaction between protein kinase Cmu and the vanilloid receptor type 1
    Yun Wang
    NCI, National Institutes of Health, Bethesda, MD 20892 4255, USA
    J Biol Chem 279:53674-82. 2004
    ..6) Mutation of S116A in rVR1 blocked both the phosphorylation of rVR1 by PKCmu and the enhancement by PKCmu of the rVR1 response to capsaicin. We conclude that PKCmu functions as a direct modulator of rVR1...
  52. ncbi request reprint Pharmacological characterization of vanilloid receptor located in the brain
    Tamas Szabo
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institute of Mental Health, Bldg 37, Room 3A01, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA
    Brain Res Mol Brain Res 98:51-7. 2002
    ..The modest differences in ligand affinities for the vanilloid receptor expressed in the brain nuclei and the dorsal root ganglion neurons may correspond to differences in sequence, modification or associated proteins...
  53. ncbi request reprint Synthetic diacylglycerols (DAG) and DAG-lactones as activators of protein kinase C (PK-C)
    Victor E Marquez
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    Acc Chem Res 36:434-43. 2003
    ..The ability to direct specific PK-C isozyme translocation with sets of structurally simple, yet highly potent molecules provides a powerful tool for engineering a plethora of molecules with novel biological functions...
  54. ncbi request reprint A novel diacylglycerol-lactone shows marked selectivity in vitro among C1 domains of protein kinase C (PKC) isoforms alpha and delta as well as selectivity for RasGRP compared with PKCalpha
    Yongmei Pu
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 280:27329-38. 2005
    ..The properties of 130C037 provide strong proof of principle for the feasibility of developing ligands with selectivity among C1 domain-containing therapeutic targets...
  55. ncbi request reprint Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes
    A Szallasi
    Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD 20892
    Brain Res 524:106-11. 1990
    ..Capsaicin inhibited binding with 10(4)-fold lower affinity than RTX, consistent with the relative in vivo potencies. The specific [3H]RTX binding appears to represent the postulated capsaicin receptor...
  56. ncbi request reprint Nonpromoting 12-deoxyphorbol 13-esters inhibit phorbol 12-myristate 13-acetate induced tumor promotion in CD-1 mouse skin
    Z Szallasi
    Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, NIH, Bethesda, Maryland 20892
    Cancer Res 53:2507-12. 1993
    ..Maximal inhibition of tumor promotion was accompanied by a block of epidermal hyperplasia; however, significant inhibition of tumor induction was observed at doses without any apparent effect on the PMA induced hyperplasia...
  57. ncbi request reprint Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper
    A Szallasi
    Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD 20892
    Neuroscience 30:515-20. 1989
    ..We conclude that resiniferatoxin acts as an ultrapotent capsaicin analog and hypothesize that it may distinguish between subclasses of capsaicin response...
  58. ncbi request reprint Differential regulation of protein kinase C isozymes by bryostatin 1 and phorbol 12-myristate 13-acetate in NIH 3T3 fibroblasts
    Z Szallasi
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892
    J Biol Chem 269:2118-24. 1994
    ..We conclude that bryostatin 1 showed substantially different regulation for PKC alpha, PKC delta, and PKC epsilon, whereas PMA distinguished only weakly between these isozymes...
  59. pmc Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human
    E Mezey
    National Institutes of Health, National Institute of Neurological Disorders and Stroke, Basic Neuroscience Program, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 97:3655-60. 2000
    ..VRs in the brain (and putative endogenous vanilloids) may be involved in the control of emotions, learning, and satiety, just to name a few exciting possibilities...
  60. ncbi request reprint Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester
    G Zhang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0580, USA
    Cell 81:917-24. 1995
    ..Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one-third of the domain, explaining how the activator promotes insertion of PKC into membranes...
  61. ncbi request reprint The cDNA sequence, expression pattern and protein characteristics of mouse protein kinase C-zeta
    J Goodnight
    Molecular Genetics Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    Gene 122:305-11. 1992
    ..When the cDNA is expressed in insect cells via a baculovirus expression vector, a 75-kDa protein is synthesized which, unlike other PKC isoforms, does not bind phorbol ester, even at very high concentrations...
  62. ncbi request reprint Effects on ligand interaction and membrane translocation of the positively charged arginine residues situated along the C1 domain binding cleft in the atypical protein kinase C isoforms
    Yongmei Pu
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 281:33773-88. 2006
    ..We speculate that the arginine residues of the C1 domain of atypical PKCs may provide an opportunity for the design of ligands selective for the atypical PKCs...
  63. ncbi request reprint Kinetics of penetration influence the apparent potency of vanilloids on TRPV1
    Jozsef Lazar
    Molecular Mechanism of Tumor Promotion, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bldg 37, Room 4048, 37 Convent Drive, MSC 4255, Bethesda, MD 20892 4255, USA
    Mol Pharmacol 69:1166-73. 2006
    ..5 nM if added simultaneously. We conclude that some vanilloids may have slow kinetics of uptake; this slow uptake may affect assessment of structure activity relations and may represent a significant factor for vanilloid drug design...
  64. ncbi request reprint [3H]Phorbol 12,13-dibutyrate binding assay for protein kinase C and related proteins
    Nancy E Lewin
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Methods Mol Biol 233:129-56. 2003
  65. pmc Wnts induce migration and invasion of myeloma plasma cells
    Ya Wei Qiang
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Blood 106:1786-93. 2005
    ..These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression...
  66. ncbi request reprint Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance
    Amy S Clark
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889, USA
    Cancer Res 63:780-6. 2003
    ..Our studies provide a rationale for targeting PKC isoforms in NSCLC cells, especially PKCdelta...
  67. ncbi request reprint The V5 domain of protein kinase C plays a critical role in determining the isoform-specific localization, translocation, and biological function of protein kinase C-delta and -epsilon
    Qiming Jane Wang
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cancer Res 2:129-40. 2004
    ..Thus, the V5 domain is critical in several of the isozyme-specific functions of PKC-delta and -epsilon...
  68. pmc Characterization of the differential roles of the twin C1a and C1b domains of protein kinase C-delta
    Yongmei Pu
    Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cancer Biology and Genetics, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 284:1302-12. 2009
    ....
  69. pmc Conformationally constrained analogues of diacylglycerol. 29. Cells sort diacylglycerol-lactone chemical zip codes to produce diverse and selective biological activities
    Dehui Duan
    Laboratory of Medicinal Chemistry, National Cancer Institute at Frederick, National Institutes of Health, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Med Chem 51:5198-220. 2008
    ..Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCalpha to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses...
  70. ncbi request reprint Branched diacylglycerol-lactones as potent protein kinase C ligands and alpha-secretase activators
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy and Department of Biochemistry and Cancer Research Institute, Seoul National University, Seoul 151 742, Korea
    J Med Chem 49:2028-36. 2006
    ..Further investigation indicated that 2 exhibited a modestly higher level of sAPPalpha secretion than did phorbol 12,13-dibutyrate (PDBu)...
  71. ncbi request reprint Alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists
    Jae Uk Chung
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 15:6043-53. 2007
    ..In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K(i)=41 and 39.2 nM and K(i(ant))=4.5 and 37 nM)...
  72. ncbi request reprint Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCalpha
    Maria Laura Garcia-Bermejo
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
    J Biol Chem 277:645-55. 2002
    ..An attractive hypothesis is that selective activation of PKC isozymes by pharmacological agents in cells can be achieved by differential intracellular targeting of each PKC...
  73. ncbi request reprint Analysis of structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as TRPV1 antagonists
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:4136-42. 2005
    ..The 2-halogen analogues showed enhanced antagonism compared to the prototype antagonist...
  74. ncbi request reprint Macrocyclic diacylglycerol-bis-lactones as conformationally constrained analogues of diacylglycerol-lactones. Interactions with protein kinase C
    Ji Hye Kang
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 47:4000-7. 2004
    ....
  75. ncbi request reprint Analysis of structure-activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:3411-20. 2004
    ..The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand...
  76. ncbi request reprint Isolation and structure of pedilstatin from a republic of maldives Pedilanthus sp
    George R Pettit
    Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State, University, Tempe 85287 2404, USA
    J Nat Prod 65:1262-5. 2002
    ..28 microg/mL, to afford, at concentrations of 2-5 microM, protection (to 80%) of human-derived lymphoblastoid CEM-SS cells from infection and cell-killing by HIV-1, and to show inhibition of protein kinase C with a K(i) of 620 +/- 20 nM...
  77. ncbi request reprint Conformationally constrained diacylglycerol (DAG) analogs: 4-C-hydroxyethyl-5-O-acyl-2,3-dideoxy-D-glyceropentono-1,4-lactone analogs as protein kinase C (PKC) ligands
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Eur J Med Chem 39:69-77. 2004
    ....
  78. ncbi request reprint Molecular determinants of vanilloid sensitivity in TRPV1
    Narender R Gavva
    Department of Neuroscience, Amgen Inc, MS 29 2 B, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
    J Biol Chem 279:20283-95. 2004
    ..Based on our data we propose a model of the TM3/4 region of TRPV1 bound to capsaicin or RTX that may aid in the development of potent TRPV1 antagonists with utility in the treatment of sensory disorders...
  79. ncbi request reprint Ligand structure-activity requirements and phospholipid dependence for the binding of phorbol esters to protein kinase D
    Qiming J Wang
    Department of Pharmacology, University of Pittsburgh, E1354 Biomedical Science Tower, Pittsburgh, PA 15261, USA
    Mol Pharmacol 64:1342-8. 2003
    ....
  80. ncbi request reprint Analysis by fluorescence resonance energy transfer of the interaction between ligands and protein kinase Cdelta in the intact cell
    Derek C Braun
    Department of Biology, Gallaudet University, Washington, D C 20002, USA
    J Biol Chem 280:8164-71. 2005
    ..The CY-PKCdelta chimera and the in vivo assays described here therefore show potential for high throughput screening of prospective PKCdelta ligands within the context of cell type...
  81. ncbi request reprint Role of phorbol ester localization in determining protein kinase C or RasGRP3 translocation: real-time analysis using fluorescent ligands and proteins
    Derek C Braun
    Department of Biology, Gallaudet University, Washington, District of Columbia, USA
    Mol Cancer Ther 4:141-50. 2005
    ....
  82. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). Effect on protein kinase C (PK-C) binding by the isosteric replacement of sn-1 and sn-2 esters in DAG-lactones
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    Bioorg Med Chem 11:2529-39. 2003
    ..The discrete K(i) analysis from the sn-1 and sn-2 isosteres further confirms that the DAG-lactones bind preferentially to the C1-domain in the sn-2 binding mode, as previously suggested...
  83. ncbi request reprint N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues: novel potent and high affinity antagonists and partial antagonists of the vanilloid receptor
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 46:3116-26. 2003
    ....
  84. ncbi request reprint New bivalent PKC ligands linked by a carbon spacer: enhancement in binding affinity
    Jayalakshmi Sridhar
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970, Reservoir Road, NW, Washington, D C 20057 2197, USA
    J Med Chem 46:4196-204. 2003
    ..The high binding affinity of compounds 2d-g to PKCs gives us the impetus to design additional molecules that would retain this enhanced activity and would also show selectivity for the PKC isoforms...
  85. ncbi request reprint Structure-activity relationships of simplified resiniferatoxin analogues with potent VR1 agonism elucidates an active conformation of RTX for VR1 binding
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:1055-69. 2004
    ..92), predicting a model of the active conformation of RTX and related vanilloids for binding to VR1. Poorer correlation was obtained between any of the conformations and the EC(50) values for calcium influx...
  86. pmc Self-assembly and lipid interactions of diacylglycerol lactone derivatives studied at the air/water interface
    Liron Philosof-Mazor
    Department of Chemistry, Ben Gurion University, Beer Sheva 84105, Israel
    Langmuir 24:11043-52. 2008
    ..Moreover, the size and charge of the phospholipid headgroups do not seem to affect DAG-lactone interactions with lipids...
  87. ncbi request reprint Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:4143-50. 2005
    ..A docking model of potent antagonist 2 with the sensor region of TRPV1 is proposed...
  88. ncbi request reprint New amide-bearing benzolactam-based protein kinase C modulators induce enhanced secretion of the amyloid precursor protein metabolite sAPPalpha
    Alan P Kozikowski
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, D C 20007 2197, USA
    J Med Chem 46:364-73. 2003
    ..Compound 5e thus becomes a viable candidate compound in the search for Alzheimer's therapeutics capable of modulating amyloid processing...
  89. ncbi request reprint Sensitization of recombinant vanilloid receptor-1 by various neurotrophic factors
    Jozsef Lazar
    Department of Physiology and Cell Physiology Research Group of the Hungarian Academy of Sciences, H 4012 Debrecen, Nagyerdei krt 98 PO Box 22, Hungary
    Life Sci 75:153-63. 2004
    ..These data argue for the putative roles of neurotrophins in inducing inflammatory (thermal) hyperalgesia via VR1...
  90. ncbi request reprint Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators
    Zhi Liang Wei
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA
    Org Lett 4:2169-72. 2002
    ..Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKC alpha...
  91. ncbi request reprint Structural basis of RasGRP binding to high-affinity PKC ligands
    Suo Bao Rong
    Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, D C 20007, USA
    J Med Chem 45:853-60. 2002
    ..Taken together, our experimental and modeling studies provide us with a better understanding of the structural basis of the binding of PKC ligands to the novel phorbol ester receptor RasGRP...
  92. ncbi request reprint Phosphorylation-dependent desensitization by anandamide of vanilloid receptor-1 (TRPV1) function in rat skeletal muscle arterioles and in Chinese hamster ovary cells expressing TRPV1
    Erzsébet Lizanecz
    Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, 4004, Debrecen, Hungary
    Mol Pharmacol 69:1015-23. 2006
    ..This property of anandamide may provide a new therapeutic strategy to manipulate TRPV1 activity...
  93. ncbi request reprint Infection of glioma cells with Sindbis virus induces selective activation and tyrosine phosphorylation of protein kinase C delta. Implications for Sindbis virus-induced apoptosis
    Avi Zrachia
    Gonda Goldschmied Medical Diagnosis Research Center, Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel
    J Biol Chem 277:23693-701. 2002
    ..We conclude that PKCdelta exerts an inhibitory effect on the apoptosis induced by SV and that phosphorylation of PKCdelta on specific tyrosines is required for this function...
  94. ncbi request reprint Synthesis and pharmacological evaluation of 8- and 9-substituted benzolactam-v8 derivatives as potent ligands for protein kinase C, a therapeutic target for Alzheimer's disease
    Ulrich R Mach
    Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S Wood St, Chicago, Illinois 60612, USA
    ChemMedChem 1:307-14. 2006
    ..An interesting decrease in binding affinity was found for the 9-thienyl analogue 13, suggesting adverse electronic interactions of the sulfur atom with PKC or parts of the cellular membrane...
  95. ncbi request reprint Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced antagonism to capsaicin
    Dong Wook Kang
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 17:214-9. 2007
    ..Compounds 23c and 31b were found to be potent full antagonists with K(i) (as functional antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively...
  96. ncbi request reprint N-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: analysis of structure-activity relationships for the "C-Region"
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:371-85. 2004
    ..Our findings indicate that 4-t-butylbenzyl is one of the most favorable groups for high receptor binding and potent antagonism to VR1 in this structural series...
  97. ncbi request reprint PKCdelta associates with and is involved in the phosphorylation of RasGRP3 in response to phorbol esters
    Chaya Brodie
    Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel
    Mol Pharmacol 66:76-84. 2004
    ..PKCdelta points to the existence of complex cross-talk between various members of the phorbol ester receptors which can have important impact on major signal transduction pathways and cellular processes induced by phorbol esters or DAG..
  98. ncbi request reprint Stereospecific high-affinity TRPV1 antagonists: chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues
    Hyungchul Ryu
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 51:57-67. 2008
    ..A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1...
  99. doi request reprint Altered calcium handling following the recombinant overexpression of protein kinase C isoforms in HaCaT cells
    Mónika Gönczi
    Department of Physiology, University of Debrecen, Debrecen, Hungary
    Exp Dermatol 17:584-91. 2008
    ..The observations also suggest that different PKC isoenzymes have different effects on the phosphatidyl-inositol signalling pathway...
  100. ncbi request reprint 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 14:2022-31. 2006
    ..7 microM. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study of 13c was carried out...