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Development of subtype-selective covalent ligands for the adenosine A2B receptor by tuning the reactive group.
Beerkens, Bert L H; Wang, Xuesong; Avgeropoulou, Maria; Adistia, Lisa N; van Veldhoven, Jacobus P D; Jespers, Willem; Liu, Rongfang; Heitman, Laura H; IJzerman, Adriaan P; van der Es, Daan.
Afiliación
  • Beerkens BLH; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • Wang X; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • Avgeropoulou M; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • Adistia LN; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • van Veldhoven JPD; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • Jespers W; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • Liu R; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • Heitman LH; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • IJzerman AP; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
  • van der Es D; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands d.van.der.es@lacdr.leidenuniv.nl.
RSC Med Chem ; 13(7): 850-856, 2022 Jul 20.
Article en En | MEDLINE | ID: mdl-35923720
ABSTRACT
Signalling through the adenosine receptors (ARs), in particular through the adenosine A2B receptor (A2BAR), has been shown to play a role in a variety of pathological conditions, ranging from immune disorders to cancer. Covalent ligands for the A2BAR have the potential to irreversibly block the receptor, as well as inhibit all A2BAR-induced signalling pathways. This will allow a thorough investigation of the pathophysiological role of the receptor. In this study, we synthesized and evaluated a set of potential covalent ligands for the A2BAR. The ligands all contain a core scaffold consisting of a substituted xanthine, varying in type and orientation of electrophilic group (warhead). Here, we find that the right combination of these variables is necessary for a high affinity, irreversible mode of binding and selectivity towards the A2BAR. Altogether, this is the case for sulfonyl fluoride 24 (LUF7982), a covalent ligand that allows for novel ways to interrogate the A2BAR.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: RSC Med Chem Año: 2022 Tipo del documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: RSC Med Chem Año: 2022 Tipo del documento: Article