| + |
CDK5 | down-regulates activity 
phosphorylation
|
DRD2 |
0.379 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259401 |
Ser321 |
GLHSTPDsPAKPEKN |
Homo sapiens |
|
| pmid |
sentence |
| 24391960 |
These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Dopaminergic Synapse |
| + |
Sumanirole maleate | up-regulates 
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207594 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
lurasidone | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257838 |
|
|
Cricetulus longicaudatus |
|
| pmid |
sentence |
| 20404009 |
In vitro functional assays demonstrated that lurasidone acts as an antagonist at D2 and 5-HT7 receptors and as a partial agonist at the 5-HT1A receptor subtype. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259462 |
|
|
Cricetulus longicaudatus |
|
| pmid |
sentence |
| 20404009 |
In vitro functional assays demonstrated that lurasidone acts as an antagonist at D2 and 5-HT7 receptors and as a partial agonist at the 5-HT1A receptor subtype. |
|
| Publications: |
2 |
Organism: |
Cricetulus Longicaudatus |
| + |
clozapine | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258368 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-2-ol | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258724 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
DRD2 | up-regulates activity
binding
|
GNAI1 |
0.503 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281583 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31142646 |
Here, we directly assess coupling between 14 representative GPCRs and 16 Gα subunits, including one wild-type Gα subunit from each of the four families and 12 chimeras with exchanged C termini. We use a sensitive bioluminescence resonance energy transfer (BRET) assay that provides control over both ligand and nucleotide binding, and allows direct comparison across G protein families. We find that the Gs- and Gq-coupled receptors we studied are relatively promiscuous and always couple to some extent to Gi1 heterotrimers. In contrast, Gi-coupled receptors are more selective. Our results with Gα subunit chimeras show that the Gα C terminus is important for coupling selectivity, but no more so than the Gα subunit core. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256701 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282043 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | Oxytocin signaling |
| + |
5-{3-[4-(2,3-Dichlorophenyl)piperidin-1-yl]propoxy}-1,3-benzothiazole | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258322 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 22025698 |
Through a robust diversity-oriented modification of the scaffold represented by aripiprazole (1), we discovered UNC9975 (2), UNC0006 (3), and UNC9994 (4) as unprecedented β-arrestin–biased D2R ligands. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DRD2 | up-regulates activity
binding
|
GNB5 |
0.617 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264993 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21303898 |
The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Dopaminergic Synapse, Oxytocin signaling |
| + |
apomorphine | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258374 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
bromocriptine | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258723 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258366 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
2 |
Organism: |
Cricetulus Griseus |
| + |
(8R)-7-propyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-13,14-diol | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258730 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
GRK6 | down-regulates activity
phosphorylation
|
DRD2 |
0.44 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279046 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26694375 |
GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
OXTR | up-regulates activity
binding
|
DRD2 |
0.37 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270333 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 27425032 |
Dopamine D2 receptor (D2R)–oxytocin receptor (OTR) interactions exist within heterocomplexes with facilitatory effects on D2R recognition and Gi/o coupling. Dopamine D2 receptor (D2R)–oxytocin receptor (OTR) interactions exist within heterocomplexes with facilitatory effects on D2R recognition and Gi/o coupling. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| Pathways: | Oxytocin signaling |
| + |
DRD2 | up-regulates activity
binding
|
GNAZ |
0.382 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281773 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257096 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
DRD2 | up-regulates activity
binding
|
GNAO1 |
0.534 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282128 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282394 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 37742189 |
Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256980 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
dopamine | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258717 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257478 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258376 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
3 |
Organism: |
Cricetulus Griseus, Homo Sapiens |
| Pathways: | Dopaminergic Synapse |
| + |
LSM-20934 | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258727 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
1-phospho-alpha-D-glucuronic acid | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258435 |
|
|
in vitro |
|
| pmid |
sentence |
| 7576010 |
The affinities of D2 receptors for agonists and antagonists were compared for receptors labeled with [1251]-7-OHPIPAT and with [*251]-NCQ-298 under conditions that promote, respectively, coupling or uncoupling of receptors to G proteins. Table 1.Similarly, the affinities of D3 receptors for quinpirole and dopamine were much higher than the affinities of D:! receptors for the agonists in the presence of Gpp(NH)p and NaCl when [1251]-NCQ-298 was used to label receptors; however, when Gpp(NH)p and NaCl were not present, and when [12sI]-7-OH-PIPAT was used, receptors bound quinpirole and dopamine with nearly equal affinities (Table 1). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
DRD2 | up-regulates activity
binding
|
GNAI3 |
0.572 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256844 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
domperidone | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258380 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258720 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
2 |
Organism: |
Cricetulus Griseus |
| + |
7-[4-[4-(2,3-Dichlorophenyl)-1,4-diazepan-1-yl]butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258321 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22025698 |
Through a robust diversity-oriented modification of the scaffold represented by aripiprazole (1), we discovered UNC9975 (2), UNC0006 (3), and UNC9994 (4) as unprecedented β-arrestin–biased D2R ligands. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
haloperidol | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258372 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
ropinirole | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258600 |
|
|
in vitro |
|
| pmid |
sentence |
| 9057850 |
Compound (R)-6, the most active compound, showed dopaminergic D2 activity and also had affinity for the 5HT1A serotonin receptor subtype. Its dopaminergic activity was more selective for the D2 receptor subtype (259-fold D2/D3 selectivity) than propylamine analogue (R)-2 (14-fold selectivity) or other dopaminergic standards (e.g., pergolide, lisuride, bromocriptine, and ropinirole, 1.0-, 3.4-, 8.7-, and 2.6-fold selectivities, respectively) |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
DRD2 | up-regulates activity
binding
|
GNAI2 |
0.565 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281772 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
2-N,6-N-Bis(2,3-dihydroxy-N-benzoyl)-L-serine amide | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258436 |
|
|
in vitro |
|
| pmid |
sentence |
| 7576010 |
D3 receptors have been reported, however, to have affinities nearly 100-fold higher than those of D2 receptors for some agonists, including (+/-)-7-hydroxy-n,n-dipropyl-aminotetralin (7-OH-DPAT) and quinpirole. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
zotepine | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258553 |
|
|
Cricetulus griseus |
|
| pmid |
sentence |
| 8935801 |
Risperidone and its active metabolite 9-OH-risperidone were compared to reference antipsychotic drugs (haloperidol, pipamperone, fluspirilene, clozapine, zotepine) and compounds under development (olanzapine, seroquel, sertindole, ORG-5222, ziprasidone) for in vitro binding to neurotransmitter receptors in brain tissue and on membranes of recombinant cells expressing cloned human receptors and for in vivo occupancy of neurotransmitter receptors in rat and guinea-pig brain following acute treatment (2 h., s.c.). The binding affinities of the compounds for various neurotransmitter receptors were measured using membrane preparations of animal brain regions and of recombinant cells expressing cloned, mostly human receptors. Receptors, tissues and cells are indicated in Table I; results are shown in Table 4A-B. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
SCH 23390 | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258732 |
|
|
Cricetulus griseus |
|
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
aripiprazole | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258319 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 22025698 |
Through a robust diversity-oriented modification of the scaffold represented by aripiprazole (1), we discovered UNC9975 (2), UNC0006 (3), and UNC9994 (4) as unprecedented β-arrestin–biased D2R ligands. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TSPAN7 | down-regulates quantity
binding
|
DRD2 |
0.25 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265557 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28223337 |
Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization.Finally, TSPAN7 negatively affects DRD2-mediated signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
chlorpromazine | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258370 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
(S)-(-)-sulpiride | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258734 |
|
|
Cricetulus griseus |
|
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
pimozide | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258719 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258378 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
2 |
Organism: |
Cricetulus Griseus |
| + |
sulpiride | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258431 |
|
|
in vitro |
|
| pmid |
sentence |
| 7576010 |
The affinities of D2 receptors for agonists and antagonists were compared for receptors labeled with [1251]-7-OHPIPAT and with [*251]-NCQ-298 under conditions that promote, respectively, coupling or uncoupling of receptors to G proteins. Table 1. When receptors were labeled with [lzs1]-NCQ-298, D2 and D3 receptors displayed similar potencies for sulpiride, a D2 receptor antagonist (Figure 3A, Table I). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
quinpirole | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258441 |
|
|
in vitro |
|
| pmid |
sentence |
| 7576010 |
D3 receptors have been reported, however, to have affinities nearly 100-fold higher than those of D2 receptors for some agonists, including (+/-)-7-hydroxy-n,n-dipropyl-aminotetralin (7-OH-DPAT) and quinpirole. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
7-[4-[4-(2,3-Dichlorophenyl)-1,4-diazepan-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258320 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 22025698 |
Through a robust diversity-oriented modification of the scaffold represented by aripiprazole (1), we discovered UNC9975 (2), UNC0006 (3), and UNC9994 (4) as unprecedented β-arrestin–biased D2R ligands. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
3-phenanthryl hydrogen sulfate | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258439 |
|
|
in vitro |
|
| pmid |
sentence |
| 7576010 |
The affinities of D2 receptors for agonists and antagonists were compared for receptors labeled with [1251]-7-OHPIPAT and with [*251]-NCQ-298 under conditions that promote, respectively, coupling or uncoupling of receptors to G proteins. Table 1. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
(R)-(+)-sulpiride | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258735 |
|
|
Cricetulus griseus |
|
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
NCS1 | down-regulates activity
binding
|
DRD2 |
0.695 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263964 |
|
|
Homo sapiens |
HEK-293 Cell, Neuron |
| pmid |
sentence |
| 12351722 |
Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Isoetharine | up-regulates activity
chemical activation
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258432 |
|
|
in vitro |
|
| pmid |
sentence |
| 7576010 |
The affinities of D2 receptors for agonists and antagonists were compared for receptors labeled with [1251]-7-OHPIPAT and with [*251]-NCQ-298 under conditions that promote, respectively, coupling or uncoupling of receptors to G proteins. Table 1. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
amisulpride | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258364 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 1975644 |
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. Table1. pharmacology of D2 and D3 receptors expressed in CHO cells. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
2-[4-[3-[2-(trifluoromethyl)-9-thioxanthenylidene]propyl]-1-piperazinyl]ethanol | down-regulates activity
chemical inhibition
|
DRD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258729 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 8301582 |
The most selective compound from this group were (+)butaclamol and domperidone which showed 5-fold D3 selectivity. A number of high affinity dopamine receptor agonists, including apomorphine and bromocriptine, also failed to demonstrate selectivity. In contrast, the natural ligand dopamine and the efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity. In the aminotetralin series, this selectivity was observed preferentially with analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series. Functional coupling of the hD3 receptor was investigated in a number of cell lines in which the hD3 receptor was stably expressed, including CHO cells, the neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
4.0
DRD2
- 
- 