Photocaging of a GPR52 agonist enables light-dependent receptor activation in cells
- Bioorg Med Chem Lett. 2027 Jan:142:130783. doi: 10.1016/j.bmcl.2026.130783.
- 1. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China.
- 2. School of Science, Harbin Institute of Technology, Shenzhen, University Town, Shenzhen 518055, China.
- 3. Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China; Shenzhen Medical Academy of Research and Translation, Shenzhen 518132, China. Electronic address: [email protected].
- 4. College of Chemistry and Materials, Institute of Flow Chemistry and Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; School of Science, Harbin Institute of Technology, Shenzhen, University Town, Shenzhen 518055, China. Electronic address: [email protected].
GPR52 is an orphan G protein-coupled receptor implicated in neuropsychiatric disorders and has attracted interest as a small-molecule drug discovery target. Here, we report the design, synthesis, and biological evaluation of photocaged derivatives of the GPR52 agonist 7d. Among the derivatives prepared, DMNB-7d showed markedly reduced basal activity in the dark and underwent photoactivation under 405 nm irradiation. In a GPR52 Tango/HTLA cell-based assay, direct irradiation of DMNB-7d-treated cells restored receptor activation, demonstrating light-dependent control of GPR52 signaling in a cellular context. Pre-irradiated DMNB-7d also showed a behavioral pharmacological effect consistent with that of the parent agonist in an MK-801-induced hyperlocomotion assay. These results identify DMNB-7d as a photoactivatable GPR52 agonist and provide a proof-of-concept strategy for developing light-responsive ligands targeting GPR52.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Neurological Disease