A Ijzerman


Affiliation: Leiden University
Country: The Netherlands


  1. Massink A, Gutiérrez de Terán H, Lenselink E, Ortiz Zacarías N, Xia L, Heitman L, et al. Sodium ion binding pocket mutations and adenosine A2A receptor function. Mol Pharmacol. 2015;87:305-13 pubmed publisher
  2. Vilums M, Zweemer A, Barmare F, van der Gracht A, Bleeker D, Yu Z, et al. When structure-affinity relationships meet structure-kinetics relationships: 3-((Inden-1-yl)amino)-1-isopropyl-cyclopentane-1-carboxamides as CCR2 antagonists. Eur J Med Chem. 2015;93:121-34 pubmed publisher
    ..The combination of SAR and SKR in the hit-to-lead process resulted in the discovery of a new high-affinity and long-residence-time CCR2 antagonist (compound 15a, Ki = 2.4 nM; RT = 714 min). ..
  3. Doornbos M, Van der Linden I, Vereyken L, Tresadern G, Ijzerman A, Lavreysen H, et al. Constitutive activity of the metabotropic glutamate receptor 2 explored with a whole-cell label-free biosensor. Biochem Pharmacol. 2018;152:201-210 pubmed publisher
  4. Vilums M, Zweemer A, Dilanchian A, van Veldhoven J, de Vries H, Brussee J, et al. Evaluation of (4-Arylpiperidin-1-yl)cyclopentanecarboxamides As High-Affinity and Long-Residence-Time Antagonists for the CCR2 Receptor. ChemMedChem. 2015;10:1249-58 pubmed publisher
    ..2 nM, t(res) =724 min) and a close analogue (Ki =7.8 nM) with a short residence time. ..
  5. Liu R, Nahon D, le Roy B, Lenselink E, Ijzerman A. Scanning mutagenesis in a yeast system delineates the role of the NPxxY(x)(5,6)F motif and helix 8 of the adenosine A(2B) receptor in G protein coupling. Biochem Pharmacol. 2015;95:290-300 pubmed publisher
    ..This study provides new insight into the molecular interplay and impact of TM7 and helix 8 for hA2B receptor activation, which may be extrapolated to other adenosine receptors and possibly to other GPCRs. ..
  6. van Veldhoven J, Liu R, Thee S, Wouters Y, Verhoork S, Mooiman C, et al. Affinity and kinetics study of anthranilic acids as HCA2 receptor agonists. Bioorg Med Chem. 2015;23:4013-25 pubmed publisher
    ..The SAR and SKR data suggest that an early compound selection based on binding kinetics is a promising addition to the lead optimization process. ..
  7. Yang X, Dong G, Michiels T, Lenselink E, Heitman L, Louvel J, et al. A covalent antagonist for the human adenosine A2A receptor. Purinergic Signal. 2017;13:191-201 pubmed publisher
    ..It may also serve as a prototype for a therapeutic approach in which a covalent antagonist may be needed to counteract prolonged and persistent presence of the endogenous ligand adenosine. ..
  8. Xia L, de Vries H, IJzerman A, Heitman L. Scintillation proximity assay (SPA) as a new approach to determine a ligand's kinetic profile. A case in point for the adenosine A1 receptor. Purinergic Signal. 2016;12:115-26 pubmed publisher
    ..Its robustness and potential for high-throughput may render this technology a preferred choice for further kinetic studies. ..
  9. Guo D, Pan A, Dror R, Mocking T, Liu R, Heitman L, et al. Molecular Basis of Ligand Dissociation from the Adenosine A2A Receptor. Mol Pharmacol. 2016;89:485-91 pubmed publisher
    ..Our results also suggest that ZM241385 follows a multistep dissociation pathway, consecutively interacting with distinct receptor regions, a mechanism that may also be common to many other GPCRs. ..

More Information


  1. Massink A, Holzheimer M, Hölscher A, Louvel J, Guo D, Spijksma G, et al. Mass spectrometry-based ligand binding assays on adenosine A1 and A2A receptors. Purinergic Signal. 2015;11:581-94 pubmed publisher
    ..The results demonstrate the feasibility of the MS binding assay, even in the absence of a deuterium-labeled internal standard, and provide great promise for the further development of label-free assays based on MS for other GPCRs. ..
  2. Lenselink E, Beuming T, van Veen C, Massink A, Sherman W, Van Vlijmen H, et al. In search of novel ligands using a structure-based approach: a case study on the adenosine A2A receptor. J Comput Aided Mol Des. 2016;30:863-874 pubmed
    ..None of these eight molecules were found to be active. Based on these results we discuss the advantages of structure-based methods and the challenges associated with finding chemically novel molecules for well-explored targets. ..
  3. Hillger J, Diehl C, Van Spronsen E, Boomsma D, Slagboom P, Heitman L, et al. Getting personal: Endogenous adenosine receptor signaling in lymphoblastoid cell lines. Biochem Pharmacol. 2016;115:114-22 pubmed publisher
    ..While further validation is needed to confirm genotype-specific effects, this set-up clearly demonstrated that LCLs are a suitable model system to study genetic influences on A2AR response in particular and GPCR responses in general. ..
  4. Guo D, Dijksteel G, van Duijl T, Heezen M, Heitman L, Ijzerman A. Equilibrium and kinetic selectivity profiling on the human adenosine receptors. Biochem Pharmacol. 2016;105:34-41 pubmed publisher
    ..Our proposed combinational strategy could be considered for future medicinal chemistry efforts and aid the design and discovery of different or even better leads for clinical applications. ..
  5. Nederpelt I, Vergroesen R, IJzerman A, Heitman L. Persistent GnRH receptor activation in pituitary αT3-1 cells analyzed with a label-free technology. Biosens Bioelectron. 2016;79:721-7 pubmed publisher
    ..Moreover, this real-time monitoring allows the examination of binding kinetics and its influence on receptor activation at a cellular level. ..
  6. Yu Z, van Veldhoven J, t Hart I, Kopf A, Heitman L, Ijzerman A. Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel. Eur J Med Chem. 2015;106:50-9 pubmed publisher
    ..1 blockers. ..
  7. Guo D, Heitman L, Ijzerman A. The Role of Target Binding Kinetics in Drug Discovery. ChemMedChem. 2015;10:1793-6 pubmed publisher
    ..In this viewpoint we explore the molecular determinants of binding kinetics and discuss challenges for future binding kinetics studies. A scheme for future kinetics-directed drug design and discovery is also proposed. ..
  8. Liu R, Wong W, Ijzerman A. Human G protein-coupled receptor studies in Saccharomyces cerevisiae. Biochem Pharmacol. 2016;114:103-15 pubmed publisher
    ..We describe 11 families of GPCRs in detail, while including the principles and developments of each yeast system applied to these different GPCRs and highlight and generalize the experimental findings of GPCR function in these systems. ..
  9. Liu R, van Veldhoven J, Ijzerman A. The role of the C-terminus of the human hydroxycarboxylic acid receptors 2 and 3 in G protein activation using Gα-engineered yeast cells. Eur J Pharmacol. 2016;770:70-7 pubmed publisher
    ..This study provides new insights into the G protein coupling profiles of the HCA receptors and the function of the receptor's C terminus, which may be extended to other GPCRs. ..
  10. van Meer B, de Vries H, Firth K, van Weerd J, Tertoolen L, Karperien H, et al. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem Biophys Res Commun. 2017;482:323-328 pubmed publisher
    ..We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS. ..
  11. Hillger J, Lieuw W, Heitman L, Ijzerman A. Label-free technology and patient cells: from early drug development to precision medicine. Drug Discov Today. 2017;22:1808-1815 pubmed publisher
    ..Applications extend as far as tissue-on-a-chip models. Thus, applying label-free technologies to patient samples can produce highly biorelevant data and, with them, unique opportunities for drug development and precision medicine. ..
  12. Guo D, Ijzerman A. Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time. Methods Mol Biol. 2018;1705:197-206 pubmed publisher
    ..We particularly focus on the molecular basis of ligand dissociation from GPCRs and provide case studies that predict ligand dissociation pathways and residence time. ..