Binding and function of estrogenic compounds toward GPER
| Compound | Agonist/Antagonista | Affinity/Efficacyb | Binding/Functionc | References |
|---|---|---|---|---|
| Kd/IC50/EC50 | ||||
| Steroids | ||||
| 17β-Estradiol | agonist | 3–6 nM | B/F | (Revankar et al., 2005; Thomas et al., 2005) |
| 17α-Estradiol | unknown | >10 μM | B/F | (Thomas et al., 2005) |
| Estrone | unknown | >>10 μM | B | (Thomas et al., 2005) |
| Estriol | antagonist | >1 μM | B/F | (Thomas et al., 2005; Lappano et al., 2010) |
| 2-Hydroxy E2 | antagonist | 0.1–1 μM | B/F | (Chourasia et al., 2015) |
| 2-Methoxy E2 | agonist | 10 nM | B | (Koganti et al., 2013) |
| Aldosterone | agonist | None detected | B/F | (Gros et al., 2011; Brailoiu et al., 2013; Cheng et al., 2014) |
| 7β-Hydroxy-epiandrosterone | antagonist | < 1 nM | F | (Sandra et al., 2012) |
| Estradiol-17β-d-glucuronide | agonist | 50 μM* | F | (Zucchetti et al., 2014) |
| Therapeutics | ||||
| 4-OHT | agonist | 0.1–1 μM | B/F | (Revankar et al., 2005; Thomas et al., 2005; Vivacqua et al., 2006a,b) |
| ICI 182,780 | agonist | 1 μM* | F | (Filardo et al., 2000) |
| Raloxifene | agonist | 100 nM* | F | (Petrie et al., 2013) |
| BT-SERMs | agonists | 10–100 nM* | F | (Abdelhamid et al., 2011) |
| DES | unknown | >1 μM | B | (Thomas et al., 2005; Pang et al., 2008) |
| Ethynylestradiol | agonist | in vivo dosing | F | (Yates et al., 2010) |
| Phytoestrogens | ||||
| Genistein | agonist | 133 nM | B/F | (Maggiolini et al., 2004; Thomas and Dong, 2006; Vivacqua et al., 2006a) |
| Oleuropein | agonist | ∼200 μM | F | (Chimento et al., 2014a) |
| Hydroxytyrosol | agonist | ∼100 μM | F | (Chimento et al., 2014a) |
| Resveratrol | agonist | ∼300 μM | F | (Dong et al., 2013) |
| Equol | agonist | 100 nM | F | (Rowlands et al., 2011) |
| Quercetin | agonist | 1 μM* | F | (Maggiolini et al., 2004) |
| Tectoridin | agonist | 10 μM* | F | (Kang et al., 2009) |
| Zearalenone | unknown | 0.8 μM | B | (Thomas et al., 2005; Thomas and Dong, 2006) |
| Daidzein | agonist | < 1 nM | F | (Kajta et al., 2013) |
| Apigenin | agonist | 20–50 μM | F | (Palmieri et al., 2012) |
| Xenoestrogens | ||||
| Atrazine | agonist | >10 μM | B/F | (Thomas and Dong, 2006; Albanito et al., 2008) |
| Bisphenol A | agonist | 0.6 μM | B/F | (Thomas and Dong, 2006; Pupo et al., 2012) |
| Nonylphenol | agonist | 0.8 μM | B/F | (Thomas and Dong, 2006) |
| Kepone | agonist | 1.4 μM | B/F | (Thomas and Dong, 2006) |
| p,p′-DDT | unknown | 2.8 μM | B | (Thomas and Dong, 2006) |
| 2,2′,5′,-PCB-4-OH | unknown | 3.8 μM | B | (Thomas and Dong, 2006) |
| o,p′-DDE | agonist | 7.1 μM | B/F | (Thomas et al., 2005; Thomas and Dong, 2006) |
| Methoxychlor | unknown | ∼10 μM | B | (Thomas and Dong, 2006) |
| p,p′-DDE | unknown | ∼10 μM | B | (Thomas and Dong, 2006) |
| o,p′-DDT | unknown | >>10 μM | B | (Thomas and Dong, 2006) |
| Synthetic Ligands | ||||
| G-1 | agonist | 7-11 nM | B/F | (Bologa et al., 2006; Dennis et al., 2009) |
| G15 | antagonist | 20 nM | B/F | (Dennis et al., 2009) |
| G36 | antagonist | ∼20 nM | F | (Dennis et al., 2011) |
| MIBE | antagonist | ∼5 μM | B/F | (Lappano et al., 2012b) |
| STX | agonist | ∼100 nM | F | (Lin et al., 2009) |
| GPER-L1 | agonist | 100 nM | B/F | (Lappano et al., 2012a) |
| GPER-L2 | agonist | 100 nM | B/F | (Lappano et al., 2012a) |
| PPT | agonist | ∼10–100 nM | F | (Petrie et al., 2013) |
| DPN | unknown | >>1 μM | F | (Petrie et al., 2013) |
↵a Reports the functional activity of the compound, where known. From studies of binding activity only, the activity is stated as unknown.
↵b Affinity/Efficacy values are based on direct (Kd) or competition (IC50) binding assays (where available) or EC50 values based on functional dose responses. In some reports, only a single dose (or limited doses) is used in functional assays, and that value (or a range for the EC50) is provided (*). Where quantitation of a dose response is not provided, the estimated value (or range) is provided (∼). None detected, indicates binding assays have been performed and no binding was detected. In vivo dosing, indicates that only functional animal studies have been carried out. >, < and > >, indicate that the half maximal response was not achieved at the indicated concentration (> indicates some effect at indicated concentration but less than 50%; > > indicates substantially less than 50% effect at stated concentration; < indicates that similar effects were observed at all doses tested and therefore it is presumed that the EC50 is below the lowest dose reported).
↵c Indicates whether the reported value is derived from a binding assay (B), functional assay (F), or has been assessed with both (B/F), with the binding constant being provided in the previous column.