T P Kenakin

Summary

Affiliation: GlaxoSmithKline Research and Development
Country: USA

Publications

  1. ncbi Ligand-selective receptor conformations revisited: the promise and the problem
    Terry Kenakin
    Systems Research, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Trends Pharmacol Sci 24:346-54. 2003
  2. ncbi Quantitation in receptor pharmacology
    T P Kenakin
    Department of Receptor Biochemistry, GlaxoSmithKline Research and Development, 5, Moore Drive, Research Triangle Park, NC 27709, USA
    Receptors Channels 7:371-85. 2001
  3. ncbi Determining the potency and molecular mechanism of action of insurmountable antagonists
    Terry Kenakin
    Department of Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    J Pharmacol Exp Ther 319:710-23. 2006
  4. doi Ligand detection in the allosteric world
    Terry P Kenakin
    Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina, USA
    J Biomol Screen 15:119-30. 2010
  5. doi Collateral efficacy as a pharmacological problem applied to new drug discovery
    Terry Kenakin
    GlaxoSmithKline, Department of Receptor Biochemistry, PO Box 13398, Research Triangle Park, NC 27709, USA
    Expert Opin Drug Discov 1:635-52. 2006
  6. pmc What systems can and can't do
    T Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    Br J Pharmacol 153:841-3. 2008
  7. ncbi Functional assays as prismatic views of drug activity: relevance to new drug discovery
    Terry Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Recept Signal Transduct Res 28:109-25. 2008
  8. ncbi Functional selectivity in GPCR modulator screening
    Terry Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research, and Development, Research Triangle Park, NC 27709, USA
    Comb Chem High Throughput Screen 11:337-43. 2008
  9. doi Seven transmembrane receptors as nature's prototype allosteric protein: de-emphasizing the geography of binding
    Terry P Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 74:541-3. 2008
  10. ncbi How pharmacological receptor theory can guide new drug discovery CCR5 HIV inhibitors in AIDS as a case study
    Terry Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, NC, USA
    Proc West Pharmacol Soc 50:1-7. 2007

Collaborators

Detail Information

Publications35

  1. ncbi Ligand-selective receptor conformations revisited: the promise and the problem
    Terry Kenakin
    Systems Research, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Trends Pharmacol Sci 24:346-54. 2003
  2. ncbi Quantitation in receptor pharmacology
    T P Kenakin
    Department of Receptor Biochemistry, GlaxoSmithKline Research and Development, 5, Moore Drive, Research Triangle Park, NC 27709, USA
    Receptors Channels 7:371-85. 2001
    ....
  3. ncbi Determining the potency and molecular mechanism of action of insurmountable antagonists
    Terry Kenakin
    Department of Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    J Pharmacol Exp Ther 319:710-23. 2006
    ....
  4. doi Ligand detection in the allosteric world
    Terry P Kenakin
    Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina, USA
    J Biomol Screen 15:119-30. 2010
    ....
  5. doi Collateral efficacy as a pharmacological problem applied to new drug discovery
    Terry Kenakin
    GlaxoSmithKline, Department of Receptor Biochemistry, PO Box 13398, Research Triangle Park, NC 27709, USA
    Expert Opin Drug Discov 1:635-52. 2006
    ..These ideas are explored, with examples, in the context of possibly more focused therapeutic application of agonists and antagonists...
  6. pmc What systems can and can't do
    T Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    Br J Pharmacol 153:841-3. 2008
    ....
  7. ncbi Functional assays as prismatic views of drug activity: relevance to new drug discovery
    Terry Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Recept Signal Transduct Res 28:109-25. 2008
    ..In AIDS, this would allow the natural chemokine systems to assist in the protection against further HIV-1 infection...
  8. ncbi Functional selectivity in GPCR modulator screening
    Terry Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research, and Development, Research Triangle Park, NC 27709, USA
    Comb Chem High Throughput Screen 11:337-43. 2008
    ..This must be balanced for allosteric potentiators with the need to retain a window to observe increased agonist effect...
  9. doi Seven transmembrane receptors as nature's prototype allosteric protein: de-emphasizing the geography of binding
    Terry P Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 74:541-3. 2008
    ..The various unique properties of allosteric modulators are discussed in the context of the increasing prevalence of allosteric ligands as investigational drugs...
  10. ncbi How pharmacological receptor theory can guide new drug discovery CCR5 HIV inhibitors in AIDS as a case study
    Terry Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, NC, USA
    Proc West Pharmacol Soc 50:1-7. 2007
    ..The allosteric properties of probe dependence and texture in antagonism are related to potential advantages in sparing of normal physiological function and reduction in susceptibility to viral resistance...
  11. doi Interrogating 7TM receptors: does texture in the question yield greater texture in the answer?
    Terry Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Recept Signal Transduct Res 29:132-9. 2009
    ..These ideas will be discussed in terms of harnessing the phenomenon of "functional selectivity" for therapeutic advantage...
  12. doi Cellular assays as portals to seven-transmembrane receptor-based drug discovery
    Terry P Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Nat Rev Drug Discov 8:617-26. 2009
    ..It also highlights how these new assays are adding value to the drug discovery process...
  13. doi '7TM receptor allostery: putting numbers to shapeshifting proteins
    Terry P Kenakin
    Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, United States
    Trends Pharmacol Sci 30:460-9. 2009
    ....
  14. pmc Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery
    Terry Kenakin
    GlaxoSmithKline, 5 Moore Drive, Mailtstop V 287, Research Triangle Park, NC 27709, USA
    Pharmacol Rev 62:265-304. 2010
    ..The explosion of technology that has enabled observation of diverse 7TMR behavior has also shown how drugs can have multiple (pluridimensional) efficacies and how this can cause paradoxical drug classification and nomenclatures...
  15. pmc Being mindful of seven-transmembrane receptor 'guests' when assessing agonist selectivity
    Terry Kenakin
    Molecular Discovery Research, GlaxoSmithKline Research, Research Triangle Park, NC 27709, USA
    Br J Pharmacol 160:1045-7. 2010
    ..As whole-cell processing of pleiotropic signalling cascades imposes cell-specific phenotypic agonist profiles, ultimately the assessment of agonist selectivity is most reliably done in the therapeutically relevant primary cell system...
  16. doi International Workshop at the Nobel Forum, Karolinska Institutet on G protein-coupled receptors: finding the words to describe monomers, oligomers, and their molecular mechanisms and defining their meaning. Can a consensus be reached?
    Terry Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    J Recept Signal Transduct Res 30:284-6. 2010
    ..This paper summarizes discussions on these topics along with a consensus definition of the term 'receptor-receptor' interaction...
  17. doi G protein coupled receptors as allosteric proteins and the role of allosteric modulators
    Terry Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    J Recept Signal Transduct Res 30:313-21. 2010
    ..Two of these behaviors (namely probe dependence for CCR5-based HIV-1 entry inhibitors and functional selectivity for biased agonism) will be highlighted with examples...
  18. doi Functional selectivity and biased receptor signaling
    Terry Kenakin
    Platform Technology Sciences, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    J Pharmacol Exp Ther 336:296-302. 2011
    ..This all poses unique challenges to the pharmacologic nomenclature of drugs, the detection and optimization of new drugs, and the association of phenotypic clinical profiles with pharmacological properties of drugs...
  19. doi Analytical pharmacology: the impact of numbers on pharmacology
    Terry Kenakin
    Platform Technology Sciences, GlaxoSmithKline Research, R T P
    Trends Pharmacol Sci 32:189-96. 2011
    ..Although some of the specifics of Black's models have been updated to account for new developments, the principles of analytical pharmacology should shape drug discovery for many years to come...
  20. ncbi Functional selectivity through protean and biased agonism: who steers the ship?
    Terry Kenakin
    Department of Biological Reagents and Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 72:1393-401. 2007
    ..Reasons are given for differentiating receptor active-state based selectivity from conventional functional organ selectivity...
  21. ncbi Allosteric agonist modulators
    Terry Kenakin
    Biochemical Reagents and Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Recept Signal Transduct Res 27:247-59. 2007
    ..The effects of such compounds in high-throughput screening assays are described as well as their effects on the dose-response curves to conventional agonists...
  22. ncbi Efficacy as a vector: the relative prevalence and paucity of inverse agonism
    Terry Kenakin
    Department of Assay Development and Compound Profiling, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 65:2-11. 2004
    ..The predominance of inverse agonism agrees with theoretical predictions which indicate that neutral antagonists are the minority species in pharmacological space...
  23. ncbi Principles: receptor theory in pharmacology
    Terry Kenakin
    Assay Development Compound Profiling, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Trends Pharmacol Sci 25:186-92. 2004
    ....
  24. ncbi G-protein coupled receptors as allosteric machines
    Terry Kenakin
    Molecular Discovery, GlaxoSmithKline Research and Development, 5 Moore Drive, RTP 27709, USA
    Receptors Channels 10:51-60. 2004
    ..Dissociation between receptor function and binding also can be encountered with allosteric ligands...
  25. ncbi Allosteric modulators: the new generation of receptor antagonist
    Terry Kenakin
    Assay Development and Compound Profiling, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    Mol Interv 4:222-9. 2004
    ..These unique properties also offer potentially useful patterns for therapeutic utility. This review summarizes methods to detect allosteric antagonism and some special properties of these receptor modulators...
  26. ncbi New concepts in drug discovery: collateral efficacy and permissive antagonism
    Terry Kenakin
    GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA
    Nat Rev Drug Discov 4:919-27. 2005
    ..Here, the design of drugs against HIV is used as an example of how these concepts might be taken into consideration for GPCR-targeted drugs in general...
  27. ncbi Receptors as microprocessors: pharmacological nuance on metabotropic glutamate receptors 1alpha
    Terry Kenakin
    Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    Sci STKE 2006:pe29. 2006
    ..Thus, ligands may not only turn receptors on and off, but may also select from their repertoire of signaling effects to further refine drug response...
  28. pmc Pharmacological onomastics: what's in a name?
    T P Kenakin
    Biochemical and Cellular Targets, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    Br J Pharmacol 153:432-8. 2008
    ..The association of distinct phenotypic behaviours with molecules opens the opportunity to better associate clinical effects with distinct pharmacological properties...
  29. ncbi Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors
    Terry Kenakin
    Department of Biochemical Reagents and Assay Development, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Trends Pharmacol Sci 28:407-15. 2007
    ....
  30. ncbi Data-driven analysis in drug discovery
    Terry Kenakin
    Assay Development, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Recept Signal Transduct Res 26:299-327. 2006
    ..Methods for the measurement of the pKB for allosteric modulators as well as co-operativity constants for these modulators is described...
  31. pmc Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules
    Celia P Briscoe
    Department of Metabolic Diseases, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Br J Pharmacol 148:619-28. 2006
    ..5. These results add further evidence to a link between GPR40 and the ability of fatty acids to acutely potentiate insulin secretion and demonstrate that small-molecule GPR40 agonists are glucose-sensitive insulin secretagogues...
  32. ncbi Peptide, peptidomimetic and small-molecule drug discovery targeting HIV-1 host-cell attachment and entry through gp120, gp41, CCR5 and CXCR4
    Wieslaw M Kazmierski
    Division of Chemistry MV CEDD, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA
    Chem Biol Drug Des 67:13-26. 2006
    ..Furthermore, such molecules enabled mechanistic elucidation of viral attachment and entry and provided additional insights toward achieving the desired drug profile...
  33. doi The relative activity of "function sparing" HIV-1 entry inhibitors on viral entry and CCR5 internalization: is allosteric functional selectivity a valuable therapeutic property?
    Vanessa M Muniz-Medina
    Infectious Diseases Discovery Performance Unit, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    Mol Pharmacol 75:490-501. 2009
    ..These data are discussed in terms of the possible benefits of sparing natural CCR5 chemokine function in HIV-1 entry inhibition treatment for AIDS involving allosteric inhibitors...
  34. ncbi New eyes to see texture in ligand efficacy
    Terry P Kenakin
    Nat Methods 2:163-4. 2005
  35. ncbi The secret lives of GPCRs
    Terry P Kenakin
    Drug Discov Today 8:674. 2003