A quest for connections : ligands for the HCA2, adenosine A3 and GPR88 receptors

Blad, C.C. (2012)

Doctoral Thesis

In this thesis, several orthosteric and allosteric agonists are presented for the newly discovered hydroxy-carboxylic acid (HCA) receptor 2, and their in vivo activity or in vitro structure-activity relationships are described. The literature on HCA receptors was also thoroughly reviewed, providing some insight into the future of this receptor family as drug targets. The anti-cancer drug N6-(2-isopentenyl)adenosine (IPA) was shown to be a specific ligand for the adenosine A3 receptor, and its antiproliferative effect seems to be mediated by this receptor at low concentrations. A ligand discovery screen for orphan receptor GPR88 was performed, in which over 4000 compounds were tested.

• Orphan receptor
• Nicotinic acid
• G protein-coupled receptor
• Atherosclerosis
• Allosteric modulator
• Adenosine
• Medicinal chemistry
• Isopentenyl adenosine
• GPR88
• GPR109A

• All authors: Blad, C.C.
• Supervisor: IJzerman, A.P.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2012-11-15
• Sponsorship: TI-Pharma, project D1-105