Birgit T Priest

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi A disubstituted succinamide is a potent sodium channel blocker with efficacy in a rat pain model
    Birgit T Priest
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    Biochemistry 43:9866-76. 2004
  2. ncbi Characterization of a new class of potent inhibitors of the voltage-gated sodium channel Nav1.7
    Brande S Williams
    Department of Ion Channels, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    Biochemistry 46:14693-703. 2007
  3. doi Imidazopyridines: a novel class of hNav1.7 channel blockers
    Clare London
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 18:1696-701. 2008
  4. pmc Subtype-selective sodium channel blockers promise a new era of pain research
    Birgit T Priest
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065, USA
    Proc Natl Acad Sci U S A 104:8205-6. 2007
  5. ncbi Blocking sodium channels to treat neuropathic pain
    Birgit T Priest
    Merck Research Laboratories, Department of Ion Channels, Rahway, NJ 07065, USA
    Expert Opin Ther Targets 11:291-306. 2007
  6. ncbi Future potential and status of selective sodium channel blockers for the treatment of pain
    Birgit T Priest
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Curr Opin Drug Discov Devel 12:682-92. 2009
  7. ncbi Role of hERG potassium channel assays in drug development
    Birgit T Priest
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
    Channels (Austin) 2:87-93. 2008
  8. doi Discovery of isoxazole voltage gated sodium channel blockers for treatment of chronic pain
    Pengcheng P Shao
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 19:5334-8. 2009
  9. ncbi A high-capacity membrane potential FRET-based assay for NaV1.8 channels
    Chou J Liu
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065, USA
    Assay Drug Dev Technol 4:37-48. 2006
  10. doi Discovery of a novel class of biphenyl pyrazole sodium channel blockers for treatment of neuropathic pain
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:7479-82. 2010

Collaborators

Detail Information

Publications36

  1. ncbi A disubstituted succinamide is a potent sodium channel blocker with efficacy in a rat pain model
    Birgit T Priest
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    Biochemistry 43:9866-76. 2004
    ..On the basis of these findings, BPBTS represents a structurally novel and potent sodium channel blocker that may be used as a template for the development of analgesic agents...
  2. ncbi Characterization of a new class of potent inhibitors of the voltage-gated sodium channel Nav1.7
    Brande S Williams
    Department of Ion Channels, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    Biochemistry 46:14693-703. 2007
    ..7 channel subtype, and with appropriate pharmacokinetic and drug metabolism properties, these compounds could be developed as analgesic agents...
  3. doi Imidazopyridines: a novel class of hNav1.7 channel blockers
    Clare London
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 18:1696-701. 2008
    ..Compound 4 had good efficacy (52% and 41% reversal of allodynia at 2 and 4h post-dose, respectively) in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain when dosed orally at 10mg/kg...
  4. pmc Subtype-selective sodium channel blockers promise a new era of pain research
    Birgit T Priest
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065, USA
    Proc Natl Acad Sci U S A 104:8205-6. 2007
  5. ncbi Blocking sodium channels to treat neuropathic pain
    Birgit T Priest
    Merck Research Laboratories, Department of Ion Channels, Rahway, NJ 07065, USA
    Expert Opin Ther Targets 11:291-306. 2007
    ..In this report, the authors review the current understanding of the role of sodium channels and of specific sodium channel subtypes in neuropathic pain signaling...
  6. ncbi Future potential and status of selective sodium channel blockers for the treatment of pain
    Birgit T Priest
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Curr Opin Drug Discov Devel 12:682-92. 2009
    ....
  7. ncbi Role of hERG potassium channel assays in drug development
    Birgit T Priest
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
    Channels (Austin) 2:87-93. 2008
    ....
  8. doi Discovery of isoxazole voltage gated sodium channel blockers for treatment of chronic pain
    Pengcheng P Shao
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 19:5334-8. 2009
    ..Substitutions on the benzylic position of benzamide were investigated to determine their effect on Na(v)1.7 inhibitory potency. The spirocyclobutyl substitution had the most significant enhancement on Na(v)1.7 inhibitory activity...
  9. ncbi A high-capacity membrane potential FRET-based assay for NaV1.8 channels
    Chou J Liu
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065, USA
    Assay Drug Dev Technol 4:37-48. 2006
    ..This highcapacity assay is sensitive to known state-dependent NaV1 modulators and can be used to identify novel and selective NaV1.8 inhibitors...
  10. doi Discovery of a novel class of biphenyl pyrazole sodium channel blockers for treatment of neuropathic pain
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:7479-82. 2010
    ..Compound 20 had outstanding efficacy in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain...
  11. ncbi Synthesis and SAR of 1,2-trans-(1-hydroxy-3-phenylprop-1-yl)cyclopentane carboxamide derivatives, a new class of sodium channel blockers
    Dong Ok
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 16:1358-61. 2006
    ..7. A benchmark compound from this series displayed efficacy in rat models of inflammatory and neuropathic pain...
  12. ncbi Sodium channel blockade may contribute to the analgesic efficacy of antidepressants
    Ivy E Dick
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey 07065 0900, USA
    J Pain 8:315-24. 2007
    ..In the current study, we compared the potency of peripheral sodium channel blockade for several tricyclic antidepressants and selective serotonin reuptake inhibitors with their therapeutic efficacy...
  13. doi Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:5536-40. 2010
    ..With a goal to develop potent peripherally active sodium channel blockers, a series of low molecular weight biaryl substituted imidazoles, oxazoles, and thiazole carboxamides were identified with good in vitro and in vivo potency...
  14. doi ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors
    William A Schmalhofer
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Mol Pharmacol 74:1476-84. 2008
    ..Thus, the (125)I-ProTx-II binding assay, described here, offers a new tool in the search for novel Na(V)1.7-selective blockers...
  15. doi 3-Amino-1,5-benzodiazepinones: potent, state-dependent sodium channel blockers with anti-epileptic activity
    SCOTT B HOYT
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, RY 123 236, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 18:1963-6. 2008
    ..One member of this series displayed subnanomolar, state-dependent sodium channel block, and was orally efficacious in a mouse model of epilepsy...
  16. doi Discovery of a novel class of isoxazoline voltage gated sodium channel blockers
    Pengcheng P Shao
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 19:5329-33. 2009
    ..Replacement of the amide with an aromatic heterocycle resulted in significant loss of sodium channel blocking activity, while non-aromatic heterocycle replacements were well tolerated...
  17. ncbi Novel cyclopentane dicarboxamide sodium channel blockers as a potential treatment for chronic pain
    Pengchang P Shao
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 15:1901-7. 2005
    ..N-Methylation on the biphenylsulfonamide side of the amide moiety significantly reduced the clearance rate in rat pharmacokinetic studies...
  18. ncbi Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion
    James Herrington
    Department of Ion Channels, Merck Research Laboratories, RY80N C31, P O Box 2000, Rahway, NJ 07065 0900, USA
    Diabetes 55:1034-42. 2006
    ..These data point to a mechanism for specific enhancement of glucose-dependent insulin secretion by applying blockers of the beta-cell I(DR), which may provide advantages over currently used therapies for the treatment of type 2 diabetes...
  19. ncbi Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats
    Richard M Brochu
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ, USA
    Mol Pharmacol 69:823-32. 2006
    ..7 microM, had no effect on cardiac electrophysiological parameters including conduction. Thus, the peripheral nerve sodium channel blocker CDA54 selectively inhibits sensory nerve signaling associated with neuropathic pain...
  20. ncbi Benzazepinone Nav1.7 blockers: potential treatments for neuropathic pain
    SCOTT B HOYT
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:6172-7. 2007
    ..A series of benzazepinones were synthesized and evaluated as hNa(v)1.7 sodium channel blockers. Several compounds from this series displayed good oral bioavailability and exposure and were efficacious in a rat model of neuropathic pain...
  21. pmc Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic beta-cells
    James Herrington
    Department of Ion Channels, Merck Research Laboratories, PO Box 2000, RY 80N C31, Rahway, NJ 07065, USA
    J Physiol 567:159-75. 2005
    ....
  22. ncbi Discovery of a novel class of benzazepinone Na(v)1.7 blockers: potential treatments for neuropathic pain
    SCOTT B HOYT
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:4630-4. 2007
    ..One member of the benzazepinone series, compound 47, displayed potent, state-dependent block of hNa(v)1.7, and was orally efficacious in a rat model of neuropathic pain...
  23. ncbi Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain
    Jun Liang
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 15:2943-7. 2005
    ....
  24. doi A novel benzazepinone sodium channel blocker with oral efficacy in a rat model of neuropathic pain
    SCOTT B HOYT
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 23:3640-5. 2013
    ..7 sodium channels. Compound 30 from this series displayed potent channel block, good selectivity versus other targets, and dose-dependent oral efficacy in a rat model of neuropathic pain...
  25. doi The inwardly rectifying potassium channel Kir1.1: development of functional assays to identify and characterize channel inhibitors
    John P Felix
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
    Assay Drug Dev Technol 10:417-31. 2012
    ..1 inhibition by different agents. All these functional Kir1.1 assays together can play an important role in supporting different aspects of drug development efforts during lead identification and/or optimization...
  26. ncbi Functional assay of voltage-gated sodium channels using membrane potential-sensitive dyes
    John P Felix
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065, USA
    Assay Drug Dev Technol 2:260-8. 2004
    ....
  27. pmc Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior
    Birgit T Priest
    Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065
    Proc Natl Acad Sci U S A 102:9382-7. 2005
    ..These results suggest that inflammatory mediators modify the function of NaV1.9 to maintain inflammation-induced hyperalgesia...
  28. pmc Ion channels as drug targets: the next GPCRs
    Gregory J Kaczorowski
    Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065, USA
    J Gen Physiol 131:399-405. 2008
  29. doi Substituted biaryl pyrazoles as sodium channel blockers
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:5480-3. 2010
    ..A series of low molecular weight biaryl substituted pyrazole carboxamides were identified with good in-vitro potency and in-vivo efficacy. Compound 26, a Nav1.7 blocker has excellent efficacy in the Chung model of neuropathic pain...
  30. ncbi ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels
    Birgit T Priest
    Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065, USA
    Toxicon 49:194-201. 2007
    ....
  31. ncbi Characterization of Kir1.1 channels with the use of a radiolabeled derivative of tertiapin
    John P Felix
    Department of Ion Channels, Merck Research Laboratories, Post Office Box 2000, Rahway, New Jersey 07065, USA
    Biochemistry 45:10129-39. 2006
    ..1 channels and suggest its utility for identifying other Kir channel modulators...
  32. ncbi Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels
    Lizhen Yan
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    Mol Pharmacol 67:1513-21. 2005
    ..Taken together, these results indicate that ShK is a potent inhibitor of Kv3.2 channels and may serve as a useful pharmacological probe for studying these channels in native preparations...
  33. ncbi A high-throughput assay for modulators of ligand-gated chloride channels
    Michel Hamelin
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Assay Drug Dev Technol 3:59-64. 2005
    ..Robust and reproducible signals were detected in response to addition of glutamate or ivermectin. This assay was used for the screening of over 180,000 samples from natural and synthetic sources...
  34. ncbi Revealing the molecular determinants of neurotoxin specificity for calcium-activated versus voltage-dependent potassium channels
    Kathleen M Giangiacomo
    Biochemistry Department, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA giang temple edu
    Biochemistry 46:5358-64. 2007
    ....
  35. ncbi A variable residue in the pore of Kv1 channels is critical for the high affinity of blockers from sea anemones and scorpions
    Bernard Gilquin
    Departement d Ingenierie et d Etudes des Proteines, Commissariat à l Energie Atomique Saclay, 91191 Gif sur Yvette Cedex, France
    J Biol Chem 280:27093-102. 2005
    ..Altogether, our data suggest that the residue at position 379 of Kv1 channels controls the affinity of a number of blocking toxins...
  36. ncbi BgK, a disulfide-containing sea anemone toxin blocking K+ channels, can be produced in Escherichia coli cytoplasm as a functional tagged protein
    Sandrine Braud
    Departement d Ingenierie et d Etudes des Proteines, CEA Saclay, 91191 Gif sur Yvette Cedex, France
    Protein Expr Purif 38:69-78. 2004
    ..8-2.8mg of purified recombinant protein per liter of culture. The recombinant peptides displayed functional properties similar to those of native BgK or BgK(F6A)...