Laura H Heitman


Affiliation: Leiden University
Country: The Netherlands


  1. Heitman L, Kleinau G, Brussee J, Krause G, Ijzerman A. Determination of different putative allosteric binding pockets at the lutropin receptor by using diverse drug-like low molecular weight ligands. Mol Cell Endocrinol. 2012;351:326-36 pubmed publisher
    ..The present study showed that these compounds are useful tools to reveal details on different allosteric binding sites located within the 7TMD of the LHCGR. ..
  2. Yu Z, Liu J, van Veldhoven J, Ijzerman A, Schalij M, Pijnappels D, et al. Allosteric Modulation of Kv11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias. Circ Arrhythm Electrophysiol. 2016;9:e003439 pubmed publisher
    ..1 blockers via pharmacological combination therapy. ..
  3. Doornbos M, Heitman L. Label-free impedance-based whole cell assay to study GPCR pharmacology. Methods Cell Biol. 2019;149:179-194 pubmed publisher
    ..Finally, we have also discussed the analysis and interpretation of the results obtained with this assay using the mGlu2 receptor as a model system. ..
  4. Hillger J, Schoop J, Boomsma D, Slagboom P, Ijzerman A, Heitman L. Whole-cell biosensor for label-free detection of GPCR-mediated drug responses in personal cell lines. Biosens Bioelectron. 2015;74:233-42 pubmed publisher
  5. Doornbos M, Vermond S, Lavreysen H, Tresadern G, Ijzerman A, Heitman L. Impact of allosteric modulation: Exploring the binding kinetics of glutamate and other orthosteric ligands of the metabotropic glutamate receptor 2. Biochem Pharmacol. 2018;155:356-365 pubmed publisher
    ..Together, this study shows the importance of studying binding kinetics in early drug discovery, as this may provide important insights towards improved efficacy in vivo. ..
  6. Ortiz Zacarías N, Lenselink E, Ijzerman A, Handel T, Heitman L. Intracellular Receptor Modulation: Novel Approach to Target GPCRs. Trends Pharmacol Sci. 2018;39:547-559 pubmed publisher
    ..Finally, the potential advantages of intracellular (allosteric) ligands over orthosteric ligands are also discussed. ..
  7. 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
  8. Soethoudt M, Hoorens M, Doelman W, Martella A, Van Der Stelt M, Heitman L. Structure-kinetic relationship studies of cannabinoid CB2 receptor agonists reveal substituent-specific lipophilic effects on residence time. Biochem Pharmacol. 2018;152:129-142 pubmed publisher
    ..This work therefore shows how CB2R agonists can be designed to have optimal kinetic profiles, which could aid the lead optimization process in drug discovery for the study or treatment of inflammatory diseases. ..
  9. Xia L, Kyrizaki A, Tosh D, van Duijl T, Roorda J, Jacobson K, et al. A binding kinetics study of human adenosine A3 receptor agonists. Biochem Pharmacol. 2018;153:248-259 pubmed publisher
    ..Our findings provide substantial evidence that, next to affinity, additional knowledge of binding kinetics is useful for developing and selecting new hA3R agonists in the early phase of the drug discovery process. ..

More Information


  1. Nederpelt I, Bunnik J, Ijzerman A, Heitman L. Kinetic Profile of Neuropeptide-Receptor Interactions. Trends Neurosci. 2016;39:830-839 pubmed publisher
  2. Bot I, Ortiz Zacarías N, de Witte W, de Vries H, Van Santbrink P, van der Velden D, et al. A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy. Sci Rep. 2017;7:52 pubmed publisher
    ..These data render 15a a promising compound for drug development and confirms high receptor occupancy as a key parameter when targeting chemokine receptors. ..
  3. Martella A, Sijben H, Rufer A, Grether U, Fingerle J, Ullmer C, et al. A Novel Selective Inverse Agonist of the CB2 Receptor as a Radiolabeled Tool Compound for Kinetic Binding Studies. Mol Pharmacol. 2017;92:389-400 pubmed publisher
    ..Altogether, this study shows that the use of a novel tool compound, i.e., [3H]RO6957022, can support the development of novel ligands with a repertoire of kinetic binding profiles for CB2R. ..
  4. Nederpelt I, Kuzikov M, de Witte W, Schnider P, Tuijt B, Gul S, et al. From receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug-action. Sci Rep. 2017;7:14169 pubmed publisher
    ..We conclude that knowledge of the relationship between in vitro drug-target binding kinetics and cellular responses is important to ultimately improve the understanding of drug efficacy in vivo. ..
  5. Xia L, de Vries H, Yang X, Lenselink E, Kyrizaki A, Barth F, et al. Kinetics of human cannabinoid 1 (CB1) receptor antagonists: Structure-kinetics relationships (SKR) and implications for insurmountable antagonism. Biochem Pharmacol. 2018;151:166-179 pubmed publisher
    ..Taken together, these findings are of importance for future design and evaluation of potent and safe hCB1 receptor antagonists. ..
  6. Hillger J, le Roy B, Wang Z, Mulder Krieger T, Boomsma D, Slagboom P, et al. Phenotypic screening of cannabinoid receptor 2 ligands shows different sensitivity to genotype. Biochem Pharmacol. 2017;130:60-70 pubmed publisher
    ..Such phenotypic screening allows early identification of compounds prone to personal differences ('precision medicine') or more suited as drugs for the general population. ..
  7. Nederpelt I, Bleeker D, Tuijt B, IJzerman A, Heitman L. Kinetic binding and activation profiles of endogenous tachykinins targeting the NK1 receptor. Biochem Pharmacol. 2016;118:88-95 pubmed publisher
    ..These findings provide new insights into the ligand-receptor interactions of tachykinins and underline the importance of measuring binding kinetics of both drug candidates and competing endogenous ligands. ..
  8. Soethoudt M, van Gils N, Van Der Stelt M, Heitman L. Protocol to Study β-Arrestin Recruitment by CB1 and CB2 Cannabinoid Receptors. Methods Mol Biol. 2016;1412:103-11 pubmed publisher
    ..We used this assay to characterize a set of reference ligands (both agonists and antagonists) on human CB1 and CB2 receptors. ..