Table 1.
NR2 Ligands with Their Main NR2 Targets, Activity Type, Reported Cellular Activity (Reporter Gene assaya, Cell Differentiation assayb, Insuline Promotor assayc), Biophysical Evidence of Binding (ITC, SPA, FP/HTRF-Based Recruitment Assay, or Cocrystal Structure), Reference and Commercial Availability.
| Structure ID | Target | Type | Reference | Biological activity/potency | CAS | Commercial availability | |
|---|---|---|---|---|---|---|---|
| Cellular | Biophysical | ||||||
| BIM5078 (1) | Antagonist | 10.1016/j.chembiol.2012.05.014109 | IC50: 0.93 μM c | Kd: 0.012 μM e | 337506-43-1 | Yes | |
| Benfluorex (2) | NR2A | Agonist | 10.1021/cb4000986108 | EC50: 24.4 μM c | n.a. | 23642-66-2 | Yes |
| Alverine citrate (3) | Agonist | EC50: 3.5-6.8 μM c | n.a. | 5560-59-8 | Yes | ||
| HNF_cpd9 (4) | Inverse Agonist | 10.3390/ijms21217895110 | IC50: 8.0 μM a | Kd: 0.30 μM f | 323-87-5 | Yes | |
| HNF_cpd10 (5) | Inverse Agonist | IC50: 24 μM a | Kd: 1.70 μM f | 365-24-2 | Yes | ||
| Bexarotene (6) | NR2B1-3 | Agonist | 10.1021/jm00044a014115 | RXRα: 0.033 μM a RXRβ: 0.024 μM a RXRγ: 0.025 μM a |
RXRα: 0.014 μM g RXRβ: 0.021 μM g RXRγ: 0.029 μM g |
153559-49-0 | Yes |
| JP3000 (7) | Agonist | 10.1021/acs.jmedchem.3c01435123 | RXRα: 0.005 μM a RXRβ: 0.0014 μM a RXRγ: 0.004 μM a |
<0.001 μM g | 3034097-74-7 | Yes | |
| Valerenic Acid (9) | Agonist | 10.1021/acs.jmedchem.8b00494131 | RXRα: 27 μM a RXRβ: 5.2 μM a RXRγ: 43 μM a |
n.a. | 3569-10-6 | Yes | |
| LG100268 (10) | Agonist | 10.1021/jm00016a018115 | RXRα: 0.004 μM a RXRβ: 0.003 μM a RXRγ: 0.004 μM a |
RXRα: 0.003 μM g RXRβ: 0.003 μM g RXRγ: 0.003 μM g |
153559-76-3 | Yes | |
| SR11237 (11) | Agonist | 10.1002/cmdc.200700265135 | RXRα: 0.029 μM a RXRβ: 0.098 μM a RXRγ: 0.232 μM a |
n.a. co-crystal: 2zy0 |
146670-40-8 | Yes | |
| UVI3003 (12) | Antagonist | 10.1073/pnas.0705356104138 | RXRb: ~0.050 μM a,j | n.a. | 847239-17-2 | Yes | |
| HX531 (13) | Antagonist | 10.1248/cpb.47.1778139 | IC50: 0.018 μM b | n.a. | 188844-34-0 | Yes | |
| Ccrp2 (15) | NR2E1 | Agonist | 10.1371/journal.pone.0099440155 | EC50: 1.0 μM a | Kd: 0.65 μM d | 958323-31-4 | Yes |
| BMS453 (17) | Agonist | 10.1016/j.chembiol.2020.07.013156 | IC50: 0.367 μM a IC50: 0.159 μM a |
Kd: ~1.0 μM i,j | 166977-43-1 | Yes | |
| Propranolol (18) | Agonist | 10.1021/acs.jmedchem.1c00733104 | EC50: 32 μM a | Kd: 0.50 μM f | 318-98-9 | Yes | |
| GFS105 (19) | Agonist | 10.1021/acs.jmedchem.1c01757102 | IC50: 0.25 μM a EC50: 0.7 μM a |
Kd: 0.50 μM f | n.a. | No | |
| 8-Phenyl- theophylline (21) |
Inverse Agonist | 10.1021/acsptsci.1c00195103 | IC50: 0.5 μM a | Kd: 0.80 μM f | 961-45-5 | Yes | |
| Photoregulin1 (22) | NR2E3 | Inverse Agonist | 10.1167/iovs.16-20177146 | IC50: 0.25 μM a | n.a. | 1003736-23-9 | Yes |
| Photoregulin3 (23) | Inverse Agonist | 10.7554/eLife.30577145 | IC50: 0.070 μM a | Kd: 64 μM f | 785708-33-0 | Yes | |
| Compound11a (24) | Agonist | 10.1016/j.bmcl.2006.07.056157 | EC50: 0.141 μM a EC50: 0.035 μM a |
n.a. | 911211-69-3 | No | |
| Biliverdin (25) | Agonist | 10.1038/s41598-022-11502-3151 | EC50: 0.005 μM a | Kd: 0.20 μM h | 856699-18-8 | Yes | |
| Cpd_C26 (26) | NR2F1 | Agonist | 10.1084/jem.20210836153 | EC50: n.a.; 1.9 f.A. @ 1 μM a EC50: n.a.; 2.4 f.A. @ 0.1 μM a |
n.a. | 374101-64-1 | Yes |
| CIA1 (27) | NR2F2 | Antagonist | 10.1126/sciadv.aaz8031154 | IC50: 3.2 μM a | n.a. | 1049691-47-5 | Yes |
| CIA2 (28) | Antagonist | IC50: 2.8 μM a | n.a. | No | |||
a
From reporter gene assay.
b
From cell differentiation assay.
c
From insulin promoter assay.
d
Kd value from DSF assays.
e
Kd value from Try/Trp fluorescence quenching assays.
f
Kd value from ITC.
g
Kd value from radioligand binding studies.
h
Kd value determined by UV absorption.
i
Kd value from FP assay.
j
No precise value reported.