gpr52 agonist ftbmt  (Takeda)

Journal: Heliyon

Article Title: Characterisation of inverse agonism of the orphan-G protein-coupled receptor GPR52 by cannabinoid ligands Cannabidiol and O-1918

doi: 10.1016/j.heliyon.2021.e07201

Figure Lengend Snippet: GPR52 inverse agonists potency.

Article Snippet: Takeda reported the first example of GPR52 agonists [ ], exemplified by Compound 7m , and subsequently reported related examples such as such as Compound [ ] and the orally bioavailable agonist FTBMT [ ], the pharmacology of which has been extensively characterised in vitro and in vivo.

Techniques:

Journal: Heliyon

Article Title: Characterisation of inverse agonism of the orphan-G protein-coupled receptor GPR52 by cannabinoid ligands Cannabidiol and O-1918

doi: 10.1016/j.heliyon.2021.e07201

Figure Lengend Snippet: Literature GPR52 agonists and inverse agonists.

Article Snippet: Takeda reported the first example of GPR52 agonists [ ], exemplified by Compound 7m , and subsequently reported related examples such as such as Compound [ ] and the orally bioavailable agonist FTBMT [ ], the pharmacology of which has been extensively characterised in vitro and in vivo.

Techniques:

Journal: Heliyon

Article Title: Characterisation of inverse agonism of the orphan-G protein-coupled receptor GPR52 by cannabinoid ligands Cannabidiol and O-1918

doi: 10.1016/j.heliyon.2021.e07201

Figure Lengend Snippet: In vitro characterisation of CBD, O-1918 and related compounds. A. CBD, O-1918 and related compounds are inverse agonists in CHO-GPR52 cells when tested alone, reducing cAMP down to the level of CHO-WT (black bar). Basal (DMSO) response from CHO-GPR52 (grey bar) is also shown for comparison, with dotted lines to indicate response level. Data are pooled (mean ± SD) from 4 independent experiments performed in duplicate, normalised to 1 μM 7m response. B. All inverse agonists inhibit an EC 50 concentration of the agonist compound 7m, reducing cAMP levels below the basal level in line with the apparent inverse agonism in A. C. All test compounds are inactive in CHO-WT cells, except for cannabidiol, which shows a small decrease in cellular cAMP beyond the standard deviation of the DMSO response (indicated by dotted lines). Data are pooled (mean ± SD) from 4 independent experiments performed in singlicate expressed as a percentage of the DMSO response.

Article Snippet: Takeda reported the first example of GPR52 agonists [ ], exemplified by Compound 7m , and subsequently reported related examples such as such as Compound [ ] and the orally bioavailable agonist FTBMT [ ], the pharmacology of which has been extensively characterised in vitro and in vivo.

Techniques: In Vitro, Comparison, Concentration Assay, Standard Deviation

Journal: Heliyon

Article Title: Characterisation of inverse agonism of the orphan-G protein-coupled receptor GPR52 by cannabinoid ligands Cannabidiol and O-1918

doi: 10.1016/j.heliyon.2021.e07201

Figure Lengend Snippet: Proposed binding modes for CBD and O-1918. A: Crystal structure of c17 (magenta) bound to GPR52, PDB code 6LI0 , water bridge between D188 ECL2 and S299 7.35 in sticks. This structure has been used for the docking experiments. Panel A is left in magenta shade to differentiate it from docking poses in grey. B: Docked pose of CBD (pale yellow) in GPR52 (grey), hydrogen bond with Asp188 ECL2 in dotted lines. C: Overlay of the proposed CBD (pale yellow) binding mode with the binding conformation of c17 from the GRP52 crystal structure (magenta). D: O-1918 (cyan) bound to GPR52 (grey) resembling the proposed CBD binding mode at B. E: O-1918 (green) bound to GPR52 (grey) with an alternate binding mode. F: O-1918 overlay of both proposed binding modes for O-1918, despite its distinct shape the molecule can bind in an almost symmetrical manner.

Article Snippet: Takeda reported the first example of GPR52 agonists [ ], exemplified by Compound 7m , and subsequently reported related examples such as such as Compound [ ] and the orally bioavailable agonist FTBMT [ ], the pharmacology of which has been extensively characterised in vitro and in vivo.

Techniques: Binding Assay