Design and characterization of an intracellular covalent ligand for CC chemokine receptor 2

Autor: Adriaan P. IJzerman, Daan van der Es, Emy Theunissen, Laura H. Heitman, Natalia V. Ortiz Zacarías, Lloyd Mallee, Tracy M. Handel, Yi Zheng, Irina Kufareva, Tereza Šimková, Cas van der Horst, Asuka Inoue, Julien Louvel, Kirti Kandhwal Chahal

Publikováno v: Journal of Medicinal Chemistry, 64(5), 2608-2621. American Chemical Society (ACS)
Journal of Medicinal Chemistry

Covalently acting inhibitors constitute a large and growing fraction of approved small-molecule therapeutics as well as useful tools for a variety of in vitro and in vivo applications. Here, we aimed to develop a covalent antagonist of CC chemokine r

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee4389804a300c8dfc34d46501d3715b
https://doi.org/10.1021/acs.jmedchem.0c01137

5′-Substituted Amiloride Derivatives as Allosteric Modulators Binding in the Sodium Ion Pocket of the Adenosine A2A Receptor

Autor: Berend J. H. Huisman, Marie Ranson, Dong Guo, Ilze Adlere, Corine van Veen, Arnault Massink, Eelke B. Lenselink, Gabrielle S. Dijksteel, Michael J. Kelso, Hayden Matthews, Benjamin J. Buckley, Adriaan P. IJzerman, Julien Louvel

Publikováno v: Journal of Medicinal Chemistry. 59:4769-4777

The sodium ion site is an allosteric site conserved among many G protein-coupled receptors (GPCRs). Amiloride 1 and 5-(N,N-hexamethylene)amiloride 2 (HMA) supposedly bind in this sodium ion site and can influence orthosteric ligand binding. The avail

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::030268a792053d795219ef15c12eb673
https://doi.org/10.1021/acs.jmedchem.6b00142

Structure-kinetics relationships of Capadenoson derivatives as adenosine A 1 receptor agonists

Autor: Laura H. Heitman, Adriaan P. IJzerman, Julien Louvel, Tamara A. M. Mocking, Marjolein Soethoudt, Thea Mulder-Krieger, Eelke B. Lenselink, Dong Guo

Publikováno v: European Journal of Medicinal Chemistry. 101:681-691

We report the synthesis and biological evaluation of new derivatives of Capadenoson, a former drug candidate that was previously advanced to phase IIa clinical trials. 19 of the 20 ligands show an affinity below 100 nM at the human adenosine A1 recep

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25f4a08ed35cf276b7811256be66fe58
https://doi.org/10.1016/j.ejmech.2015.07.023

A covalent antagonist for the human adenosine A2A receptor

Autor: Thomas J M Michiels, Laura H. Heitman, Xue Yang, Julien Louvel, Ad P. IJzerman, Eelke B. Lenselink, Guo Dong

Publikováno v: Purinergic signalling, 13(2), 191-201
Purinergic Signalling, 13(2), 191-201. SPRINGER
Purinergic Signalling, 13(2), 191-201
Purinergic signalling

The structure of the human A2A adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive mo

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::313d0b8828eaed6bc6f96956526f217f
https://hdl.handle.net/1887/64259

Removal of Human Ether-à-go-go Related Gene (hERG) K+ Channel Affinity through Rigidity: A Case of Clofilium Analogues

Autor: Elisabeth Klaasse, Johannes Brussee, João F. S. Carvalho, Eelke B. Lenselink, Julien Louvel, Marjolein Soethoudt, Adriaan P. IJzerman, Zhiyi Yu

Publikováno v: Journal of Medicinal Chemistry. 56:9427-9440

Cardiotoxicity is a side effect that plagues modern drug design and is very often due to the off-target blockade of the human ether-à-go-go related gene (hERG) potassium channel. To better understand the structural determinants of this blockade, we

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bac0ddd9cffdc2d208621e6ac626c36
https://doi.org/10.1021/jm4010434