Iwan J P De Esch

Summary

Publications

  1. pmc Design, synthesis, and structure-activity relationships of highly potent 5-HT₃ receptor ligands
    Mark H P Verheij
    Leiden Amsterdam Center of Drug Research LACDR, Amsterdam Institute for Molecules Medicines and Systems AIMMS, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, Amsterdam, The Netherlands
    J Med Chem 55:8603-14. 2012
  2. pmc Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain
    Atilla Akdemir
    Division of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
    Bioorg Med Chem 20:5992-6002. 2012
  3. pmc Fragment library screening reveals remarkable similarities between the G protein-coupled receptor histamine H₄ and the ion channel serotonin 5-HT₃A
    Mark H P Verheij
    Leiden Amsterdam Center of Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem Lett 21:5460-4. 2011
  4. doi request reprint High-resolution bioactivity profiling of mixtures toward the acetylcholine binding protein using a nanofractionation spotter technology
    Jeroen Kool
    BioMolecular Analysis, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, Amsterdam, The Netherlands
    J Biomol Screen 16:917-24. 2011
  5. doi request reprint Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists
    Rogier A Smits
    Griffin Discoveries BV, Department of Medicinal Chemistry, Room P 246, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 53:2390-400. 2010
  6. doi request reprint Surface plasmon resonance biosensor based fragment screening using acetylcholine binding protein identifies ligand efficiency hot spots (LE hot spots) by deconstruction of nicotinic acetylcholine receptor α7 ligands
    Gerdien E de Kloe
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 53:7192-201. 2010
  7. pmc Pharmacological characterization of the new histamine H4 receptor agonist VUF 8430
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
    Br J Pharmacol 157:34-43. 2009
  8. doi request reprint Ligand based design of novel histamine H₄ receptor antagonists; fragment optimization and analysis of binding kinetics
    Rogier A Smits
    Griffin Discoveries BV, Department of Medicinal Chemistry, Room P 246, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem Lett 22:461-7. 2012
  9. ncbi request reprint Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach
    Rogier A Smits
    Department of Pharmacochemistry, Faculty of Exact Sciences, Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 51:7855-65. 2008
  10. doi request reprint Molecular determinants of ligand binding to H4R species variants
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, VU University Amsterdam, Amsterdam, The Netherlands
    Mol Pharmacol 77:734-43. 2010

Collaborators

Detail Information

Publications62

  1. pmc Design, synthesis, and structure-activity relationships of highly potent 5-HT₃ receptor ligands
    Mark H P Verheij
    Leiden Amsterdam Center of Drug Research LACDR, Amsterdam Institute for Molecules Medicines and Systems AIMMS, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, Amsterdam, The Netherlands
    J Med Chem 55:8603-14. 2012
    ..The observed SAR is in agreement with established pharmacophore models for 5-HT₃ ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches...
  2. pmc Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain
    Atilla Akdemir
    Division of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
    Bioorg Med Chem 20:5992-6002. 2012
    ....
  3. pmc Fragment library screening reveals remarkable similarities between the G protein-coupled receptor histamine H₄ and the ion channel serotonin 5-HT₃A
    Mark H P Verheij
    Leiden Amsterdam Center of Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem Lett 21:5460-4. 2011
    ....
  4. doi request reprint High-resolution bioactivity profiling of mixtures toward the acetylcholine binding protein using a nanofractionation spotter technology
    Jeroen Kool
    BioMolecular Analysis, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, Amsterdam, The Netherlands
    J Biomol Screen 16:917-24. 2011
    ....
  5. doi request reprint Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists
    Rogier A Smits
    Griffin Discoveries BV, Department of Medicinal Chemistry, Room P 246, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 53:2390-400. 2010
    ..In vivo evaluation of the potent 2-(6-chloro-2-(4-methylpiperazin-1-yl)quinazoline-4-amino)-N-phenylethanesulfonamide (54) (pK(i) = 8.31 +/- 0.10) revealed it to have anti-inflammatory activity in an animal model of acute inflammation...
  6. doi request reprint Surface plasmon resonance biosensor based fragment screening using acetylcholine binding protein identifies ligand efficiency hot spots (LE hot spots) by deconstruction of nicotinic acetylcholine receptor α7 ligands
    Gerdien E de Kloe
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 53:7192-201. 2010
    ..These hot spots can be used to identity the most promising hit fragments in a large scale fragment library screen...
  7. pmc Pharmacological characterization of the new histamine H4 receptor agonist VUF 8430
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
    Br J Pharmacol 157:34-43. 2009
    ..We compare the pharmacological profiles of a new histamine H4 receptor agonist 2-(2-guanidinoethyl)isothiourea (VUF 8430) with that of a previously described H4 receptor agonist, 4-methylhistamine...
  8. doi request reprint Ligand based design of novel histamine H₄ receptor antagonists; fragment optimization and analysis of binding kinetics
    Rogier A Smits
    Griffin Discoveries BV, Department of Medicinal Chemistry, Room P 246, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem Lett 22:461-7. 2012
    ..Analysis of its binding kinetics at the human H(4)R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120...
  9. ncbi request reprint Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach
    Rogier A Smits
    Department of Pharmacochemistry, Faculty of Exact Sciences, Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 51:7855-65. 2008
    ..Compounds from this novel series of quinazolines are antagonists at the rat H(4)R and were found to possess anti-inflammatory properties in vivo in the rat...
  10. doi request reprint Molecular determinants of ligand binding to H4R species variants
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, VU University Amsterdam, Amsterdam, The Netherlands
    Mol Pharmacol 77:734-43. 2010
    ..Our results are a useful reference for ligand selection for studies in animal models of diseases and offer new insights in the understanding of H(4)R-ligand receptor interactions...
  11. doi request reprint Acetylcholine binding protein (AChBP) as template for hierarchical in silico screening procedures to identify structurally novel ligands for the nicotinic receptors
    Atilla Akdemir
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, The Netherlands
    Bioorg Med Chem 19:6107-19. 2011
    ....
  12. doi request reprint Molecular determinants of ligand binding modes in the histamine H(4) receptor: linking ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models to in silico guided receptor mutagenesis studies
    Enade P Istyastono
    Department of Pharmacochemistry, Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 54:8136-47. 2011
    ..Our ligand-steered, experimentally supported protein modeling method gives new insights into ligand recognition by H(4)R and can be used as a general approach to elucidate the structure of protein-ligand complexes...
  13. ncbi request reprint Online fluorescence enhancement assay for the acetylcholine binding protein with parallel mass spectrometric identification
    Jeroen Kool
    BioMolecular Analysis, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081HV Amsterdam, The Netherlands
    J Med Chem 53:4720-30. 2010
    ..This led to the possibility of affinity ranking of ligands in mixtures with parallel high-resolution mass spectrometry for compound identification...
  14. doi request reprint Identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor US28
    Henry F Vischer
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Bioorg Med Chem 18:675-88. 2010
    ..Novel nonpeptidergic chemotypes were identified as neutral antagonists or inverse agonists on US28, that allosterically inhibit chemokine binding to US28...
  15. doi request reprint Identification of overlapping but differential binding sites for the high-affinity CXCR3 antagonists NBI-74330 and VUF11211
    Danny J Scholten
    Division of Medicinal Chemistry, Faculty of Science, Amsterdam Institute for Molecules, Medicines, and Systems, VU University Amsterdam, Amsterdam, The Netherlands
    Mol Pharmacol 85:116-26. 2014
    ..Altogether, in this study, we show overlapping, yet different binding sites for two high-affinity CXCR3 antagonists, which offer new opportunities for the structure-based design of allosteric modulators for CXCR3. ..
  16. doi request reprint 4-benzyl-1H-imidazoles with oxazoline termini as histamine H3 receptor agonists
    Maikel Wijtmans
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 51:2944-53. 2008
    ..Our findings further substantiate the growing notion that basic ligand sidechains are not necessary for H 3R activation and reveal the oxazolino group as a hitherto unexplored functional group in H3R research...
  17. doi request reprint Small and colorful stones make beautiful mosaics: fragment-based chemogenomics
    Chris de Graaf
    Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems AIMMS, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Drug Discov Today 18:323-30. 2013
    ..With a wealth of fragment screening data being generated in industry and academia, such approaches will contribute to a more detailed structural understanding of ligand-protein interactions...
  18. doi request reprint Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein
    Ewald Edink
    Leiden Amsterdam Center of Drug Research, Division of Medicinal Chemistry, Amsterdam Institute for Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands
    Bioorg Med Chem Lett 22:1448-54. 2012
    ..The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes...
  19. doi request reprint A novel series of histamine H4 receptor antagonists based on the pyrido[3,2-d]pyrimidine scaffold: comparison of hERG binding and target residence time with PF-3893787
    Mounir Andaloussi
    Griffin Discoveries BV, Department of Medicinal Chemistry, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem Lett 23:2663-70. 2013
    ..Overall, the pyrido[3,2-d]pyrimidines show an excellent in vitro profile that warrants their further investigation in relevant models of human disease...
  20. ncbi request reprint Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives
    Rogier A Smits
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 49:4512-6. 2006
    ..On the basis of the derived structure-activity relationships and additional pharmacological results, a pharmacophore model was constructed, which will be the premise for the design of novel H4R ligands...
  21. ncbi request reprint N-substituted piperidinyl alkyl imidazoles: discovery of methimepip as a potent and selective histamine H3 receptor agonist
    Ruengwit Kitbunnadaj
    Faculty of Chemistry, Department of Pharmacochemistry, Division of Medicinal Chemistry, Leiden Amsterdam Center of Drug Research, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 48:2100-7. 2005
    ..26). Moreover, in vivo microdialysis (in rat brain) showed that methimepip reduces the basal level of brain histamine to about 25% after a 5 mg/kg intraperitoneal administration...
  22. ncbi request reprint A chemical switch for the modulation of the functional activity of higher homologues of histamine on the human histamine H3 receptor: effect of various substitutions at the primary amino function
    Marinella Govoni
    Leiden Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 49:2549-57. 2006
    ..1 and 8.4, respectively). A very potent and selective H(3)R agonist (1l, pEC(50) = 8.9, alpha = 0.94) and a very potent, though not highly selective, H(3)R inverse agonist (2k, pIC(50) = 8.9, alpha = -0.97) have been identified as well...
  23. ncbi request reprint Synthesis and pharmacological characterization of novel inverse agonists acting on the viral-encoded chemokine receptor US28
    Janneke W Hulshof
    Leiden Amsterdam Center for Drug Research, LACDR, Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem 14:7213-30. 2006
    ..These novel inverse agonists serve as valuable tools to elucidate the role of constitutive signaling in the pathogenesis of viral infection and may have therapeutic potential as leads for new antiviral drugs...
  24. doi request reprint Clobenpropit analogs as dual activity ligands for the histamine H3 and H4 receptors: synthesis, pharmacological evaluation, and cross-target QSAR studies
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem 17:3987-94. 2009
    ..QSAR models have been generated in order to explain the H(3)R and H(4)R affinities...
  25. doi request reprint Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo
    Rogier A Smits
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 51:2457-67. 2008
    ..In vivo studies in the rat reveal that compound 57 has significant anti-inflammatory properties in the carrageenan-induced paw-edema model...
  26. ncbi request reprint The emerging role of the histamine H4 receptor in anti-inflammatory therapy
    Herman D Lim
    Division of Medicinal Chemistry, Faculty of Sciences, Leiden Amsterdam Center of Drug Research, LACDR, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Curr Top Med Chem 6:1365-73. 2006
    ..In this review, we describe the receptor protein, its putative role in (patho)physiology and the latest ligands that are being developed to explore the feasibility of the H(4) receptor as a drug target...
  27. doi request reprint Phenylalanine 169 in the second extracellular loop of the human histamine H4 receptor is responsible for the difference in agonist binding between human and mouse H4 receptors
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Pharmacol Exp Ther 327:88-96. 2008
    ..These results point to an important role of the second extracellular loop in the agonist binding to the H(4) receptor and provide a molecular explanation for the species difference between human and mouse H(4) receptors...
  28. ncbi request reprint Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist
    Herman D Lim
    Leiden Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 49:6650-1. 2006
    ..This nonimidazole ligand is introduced as a useful and complementary pharmacological tool that enables further unraveling of the physiological roles of the H4 receptor...
  29. doi request reprint KLIFS: a knowledge-based structural database to navigate kinase-ligand interaction space
    Oscar P J van Linden
    Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems AIMMS, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 57:249-77. 2014
    ..These analyses lead to an improved understanding of the structural requirements of kinase binding that will be useful in ligand discovery and design studies. ..
  30. doi request reprint Triazole ligands reveal distinct molecular features that induce histamine H4 receptor affinity and subtly govern H4/H3 subtype selectivity
    Maikel Wijtmans
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 54:1693-703. 2011
    ..Computational evidence is provided to account for two key selectivity switches and to pinpoint a lipophilic pocket as an important handle for H(4)R over H(3)R selectivity...
  31. doi request reprint From heptahelical bundle to hits from the Haystack: structure-based virtual screening for GPCR ligands
    Albert J Kooistra
    Division of Medicinal Chemistry, Faculty of Sciences, Leiden Amsterdam Center for Drug Research LACDR, VU University Amsterdam, De Boelelaan, Amsterdam, The Netherlands
    Methods Enzymol 522:279-336. 2013
    ..Moreover, the recently solved GPCR crystal structures have further increased the opportunities in structure-based ligand discovery for this pharmaceutically important protein family...
  32. doi request reprint Fragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis
    Ewald Edink
    Leiden Amsterdam Center of Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, The Netherlands
    J Am Chem Soc 133:5363-71. 2011
    ..This study illustrates that thermodynamic analysis provides valuable information on ligand binding modes and is complementary to affinity data when guiding rational structure- and fragment-based discovery approaches...
  33. ncbi request reprint Towards small-molecule CXCR3 ligands with clinical potential
    Maikel Wijtmans
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    ChemMedChem 3:861-72. 2008
    ..One of the compounds, AMG487, progressed to Phase II clinical trials but has been withdrawn because of lack of efficacy. New antagonist classes are being developed to reveal the full therapeutic potential of CXCR3...
  34. ncbi request reprint Synthesis and structure-activity relationships of 3H-quinazolin-4-ones and 3H-pyrido[2,3-d]pyrimidin-4-ones as CXCR3 receptor antagonists
    Stefania Storelli
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
    Arch Pharm (Weinheim) 340:281-91. 2007
    ..The described molecules serve as tool to investigate the role of the CXCR3 receptor in various inflammatory conditions...
  35. doi request reprint Use of acetylcholine binding protein in the search for novel alpha7 nicotinic receptor ligands. In silico docking, pharmacological screening, and X-ray analysis
    Chris Ulens
    Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Med Chem 52:2372-83. 2009
    ..The analysis of the dual binding mode of these dibenzosuberyl-containing compounds can lead to better understanding of the complex mode of action of similar tricyclic ligands on Cys-loop receptors...
  36. ncbi request reprint Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28
    Janneke W Hulshof
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 48:6461-71. 2005
    ..These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection...
  37. doi request reprint Chemical subtleties in small-molecule modulation of peptide receptor function: the case of CXCR3 biaryl-type ligands
    Maikel Wijtmans
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, The Netherlands
    J Med Chem 55:10572-83. 2012
    ....
  38. pmc Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure
    Chimed Jansen
    Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems AIMMS, VU University Amsterdam, Amsterdam, The Netherlands
    J Med Chem 56:2087-96. 2013
    ..This approach identified six novel TbrPDEB1 inhibitors with IC50 values of 10-80 μM, which may be further optimized as potential selective TbrPDEB inhibitors...
  39. ncbi request reprint New high affinity H3 receptor agonists without a basic side chain
    Ruengwit Kitbunnadaj
    Leiden Amsterdam Center of Drug Research LACDR, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit Amsterdam, The Netherlands
    Bioorg Med Chem 13:6309-23. 2005
    ..0 and pEC(50) = 8.1) with a 320-fold selectivity at the human H(3) receptor over the human H(4) receptor...
  40. ncbi request reprint Major advances in the development of histamine H4 receptor ligands
    Rogier A Smits
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Drug Discov Today 14:745-53. 2009
    ..Taken together, the histamine H4R field is gearing up for clinical studies and has the potential to deliver another generation of blockbuster drugs...
  41. pmc Molecular and biochemical pharmacology of the histamine H4 receptor
    Rob Leurs
    Department of Medicinal Chemistry, Leiden Amsterdam Center for Drug Research, VU University Amsterdam, Amsterdam, The Netherlands
    Br J Pharmacol 157:14-23. 2009
    ..In this review, we summarize the historical developments and the molecular and biochemical pharmacology of the H4 receptor...
  42. doi request reprint Delineation of agonist binding to the human histamine H4 receptor using mutational analysis, homology modeling, and ab initio calculations
    Aldo Jongejan
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Chem Inf Model 48:1455-63. 2008
    ..These studies provide a molecular understanding for the action of a variety of H 4 receptor-ligands. The resulting H 4 receptor model will be the basis for the development of new H 4 receptor-ligands...
  43. doi request reprint Exploring a pocket for polycycloaliphatic groups in the CXCR3 receptor with the aid of a modular synthetic strategy
    Maikel Wijtmans
    Division of Medicinal Chemistry, Faculty of Sciences, Leiden Amsterdam Center for Drug Research, VU University Amsterdam, Amsterdam, The Netherlands
    Bioorg Med Chem Lett 19:2252-7. 2009
    ..A CXCR3 pocket capable of accommodating polycycloaliphatics was explored using a modular synthetic strategy. The systematic studies reveal that the tricyclic 2-adamantane and bicyclic (iso)bornyl group are efficiently recognized by CXCR3...
  44. ncbi request reprint Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists
    Nalan Terzioglu
    Istanbul University, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 34452 Istanbul, Turkey
    Bioorg Med Chem Lett 14:5251-6. 2004
    ..The ligands have been evaluated by radioligand displacement studies and functional assays for their interaction with both the human histamine H(3) and H(4) receptors and exhibit pK(i) values up to 7.5 at the human H(4)R...
  45. doi request reprint Several down, a few to go: histamine H3 receptor ligands making the final push towards the market?
    Sebastiaan Kuhne
    VU University Amsterdam, Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Expert Opin Investig Drugs 20:1629-48. 2011
    ..Blocking the H(3)R with antagonists/inverse agonists has been postulated to be of broad therapeutic use. Indeed, H(3)R antagonists/inverse agonists have been extensively evaluated in the clinic...
  46. pmc Development of a microfluidic confocal fluorescence detection system for the hyphenation of nano-LC to on-line biochemical assays
    Ferry Heus
    BioMolecular Analysis, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Anal Bioanal Chem 398:3023-32. 2010
    ..Finally, coupling of the detection system to gradient reversed-phase nano-LC allowed analysis of mixtures in order to identify the bioactive compounds present by injecting 10 nL of each mixture...
  47. doi request reprint CXCR3 antagonists: quaternary ammonium salts equipped with biphenyl- and polycycloaliphatic-anchors
    Maikel Wijtmans
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Bioorg Med Chem 19:3384-93. 2011
    ..This led to the identification of several bisaryl-based ligands with CXCR3 affinities of around 100 nM and with the ability to antagonize the functional activity of CXCL10...
  48. pmc Targeted LC-MS derivatization for aldehydes and carboxylic acids with a new derivatization agent 4-APEBA
    Mark Eggink
    Section of Biomolecular Analysis, Faculty of Science, VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Anal Bioanal Chem 397:665-75. 2010
    ....
  49. ncbi request reprint From three-dimensional GPCR structure to rational ligand discovery
    Albert J Kooistra
    Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems AIMMS, VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Adv Exp Med Biol 796:129-57. 2014
    ....
  50. pmc Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor
    Chris de Graaf
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 54:8195-206. 2011
    ..Of the 26 tested fragments, 19 compounds had affinities ranging from 10 μM to 6 nM. The current study shows the potential of in silico screening against GPCR crystal structures to explore novel, fragment-like GPCR ligand space...
  51. pmc Noncompetitive antagonism and inverse agonism as mechanism of action of nonpeptidergic antagonists at primate and rodent CXCR3 chemokine receptors
    Dennis Verzijl
    Leiden Amsterdam Center of Drug Research, Faculty of Science, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Pharmacol Exp Ther 325:544-55. 2008
    ..35A. TAK-779 shows weak partial inverse agonism at CXCR3 N3.35A, and it probably has a different mode of interaction with CXCR3 than the other two classes of small-molecule inverse agonists...
  52. ncbi request reprint The role and application of in silico docking in chemical genomics research
    Aldo Jongejan
    Division of Medicinal Chemistry, Leiden Amsterdam Center for Drug Research, Faculty of Sciences, Vrije Universiteit, Amsterdam, The Netherlands
    Methods Mol Biol 310:63-91. 2005
    ..We also cover the analysis and rescoring of the obtained docking poses. Possible pitfalls in the docking studies are discussed and hints are provided to resolve commonly occurring problems...
  53. ncbi request reprint Molecular determinants of selective agonist and antagonist binding to the histamine H₄ receptor
    Enade P Istyastono
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Curr Top Med Chem 11:661-79. 2011
    ....
  54. ncbi request reprint Regiochemistry of the condensation of 2-aroyl-cyclohexanones and 2-cyanoacetamide: 13C-labeling studies and semiempirical MO calculations
    Oscar P J van Linden
    Leiden Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Org Chem 77:7355-63. 2012
    ..Our results facilitate synthetic access to a range of these interesting synthetic intermediates...
  55. doi request reprint Development of surface plasmon resonance biosensor assays for primary and secondary screening of acetylcholine binding protein ligands
    Kim Retra
    Leiden Amsterdam Center for Drug Research, Division of BioMolecular Analysis, Faculty of Sciences, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
    Anal Biochem 407:58-64. 2010
    ..96. Using both assays, we identified the compound tacrine as a ligand for AChBP...
  56. doi request reprint En route to new blockbuster anti-histamines: surveying the offspring of the expanding histamine receptor family
    Rob Leurs
    Leiden Amsterdam Center for Drug Research, Medicinal Chemistry, Faculty of Science, VU University Amsterdam, Amsterdam, The Netherlands
    Trends Pharmacol Sci 32:250-7. 2011
    ..Several new anti-histamines are now being tested for diverse clinical applications and are poised to become the next blockbuster drugs targeting histamine receptors...
  57. doi request reprint Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase
    Oscar P J van Linden
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Eur J Med Chem 47:493-500. 2012
    ..The results underscore the strength of fragment based in silico screening as a tool for the discovery of novel lead compounds as small molecule kinase inhibitors...
  58. ncbi request reprint Synthesis and structure-activity relationship of 3-phenyl-3H-quinazolin-4-one derivatives as CXCR3 chemokine receptor antagonists
    Stefania Storelli
    Leiden Amsterdam Center for Drug Research LACDR, Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, The Netherlands
    Bioorg Med Chem Lett 15:2910-3. 2005
    ..The most potent compound (1d) has been evaluated using radioligand binding and calcium mobilization assays and is considered a useful tool for further characterization of the CXCR3 receptor...
  59. doi request reprint Catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase B1
    Kristina M Orrling
    Leiden Amsterdam Centre of Drug Research LACDR, Amsterdam Institute of Molecules, Medicines and Systems AIMMS, Division of Medicinal Chemistry, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 55:8745-56. 2012
    ..Our findings further validate the TbrPDEB family as antitrypanosomal target...
  60. ncbi request reprint The histamine H3 receptor: from gene cloning to H3 receptor drugs
    Rob Leurs
    Division of Medicinal Chemistry, Leiden Amsterdam Center for Drug Research, Vrije Universiteit Amsterdam, Faculty of Science, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Nat Rev Drug Discov 4:107-20. 2005
    ..Here, we discuss relevant information on this target protein and describe the development of various H(3) receptor agonists and antagonists, and their effects in preclinical animal models...
  61. ncbi request reprint Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists
    Ruengwit Kitbunnadaj
    Leiden Amsterdam Center of Drug Research LACDR, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 46:5445-57. 2003
    ..Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H(3) and H(4) receptor...
  62. doi request reprint Nanofractionation spotter technology for rapid contactless and high-resolution deposition of LC eluent for further off-line analysis
    Jeroen Kool
    BioMolecular Analysis, Department of Chemistry and Pharmaceutical Sciences, and FMI Bèta VU, ELE Bèta VU Mechanical and Electronic Engineering, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081HV Amsterdam, The Netherlands
    Anal Chem 83:125-32. 2011
    ....