Laura H Heitman
Affiliation: Leiden University
Country: The Netherlands
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Soethoudt M, van Gils N, Van Der Stelt M, Heitman L. Protocol to Study Î²-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. ..