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D2 receptor

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Target id: 215

Nomenclature: D2 receptor

Family: Dopamine receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 443 11q23.2 DRD2 dopamine receptor D2 8,44
Mouse 7 444 9 26.72 cM Drd2 dopamine receptor D2 86
Rat 7 444 8q23 Drd2 dopamine receptor D2 8,23
Gene and Protein Information Comments
The human D2 receptor exists as two alternatively spliced isoforms [43]. The 443 amino acid receptor is the long form (D2L). The short form (D2S) is 414 amino acids long.
Previous and Unofficial Names Click here for help
D2A and D2B | D2R | dopamine D2 receptor | dopamine receptor 2 | D2 receptor | D2(415) and D2(444)
Database Links Click here for help
Specialist databases
GPCRdb drd2_human (Hs), drd2_mouse (Mm), drd2_rat (Rn)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone
PDB Id:  6CM4
Ligand:  risperidone
Resolution:  2.9Å
Species:  Human
References:  130
Natural/Endogenous Ligands Click here for help
dopamine

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
rotigotine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 10.2 pKi 36
pKi 10.2 (Ki 6x10-11 M) [36]
aripiprazole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 9.7 pKi 102
pKi 9.7 [102]
brexpiprazole Small molecule or natural product Approved drug Hs Partial agonist 9.5 pKi 74
pKi 9.5 (Ki 3x10-10 M) [74]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 9.2 – 9.5 pKi 84
pKi 9.2 – 9.5 [84]
aripiprazole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 9.1 pKi 136
pKi 9.1 (Ki 8x10-10 M) [136]
cabergoline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 9.0 – 9.2 pKi 84
pKi 9.0 – 9.2 [84]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 9.1 pKi 84
pKi 9.1 [84]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 8.6 pKi 84
pKi 8.6 [84]
UNC9975 Small molecule or natural product Hs Biased agonist 8.6 pKi 3
pKi 8.6 (Ki 2.6x10-9 M) [3]
Description: β-arrestin 2 biased agonist.
UNC0006 Small molecule or natural product Hs Biased agonist 8.3 pKi 3
pKi 8.3 (Ki 5x10-9 M) [3]
Description: β-arrestin 2 biased agonist.
cariprazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.2 pKi 1
pKi 8.2 (Ki 5.7x10-9 M) [1]
Description: Binding affinity to human dopamine D2L receptor
MLS1547 Small molecule or natural product Hs Biased agonist 8.2 pKi 39
pKi 8.2 (Ki 5.9x10-9 M) [39]
Description: Biased agonist for G-protein coupling to Gi.
(-)-N-porphynorapomorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.5 – 8.9 pKi 40,100
pKi 7.5 – 8.9 [40,100]
ropinirole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 8.1 pKi 48
pKi 8.1 (Ki 7.2x10-9 M) [48]
LP-44 Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.1 pKi 69
pKi 8.1 (Ki 7.3x10-9 M) [69]
sumanirole Small molecule or natural product Hs Full agonist 8.1 pKi 81
pKi 8.1 (Ki 9x10-9 M) [81]
bromocriptine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.3 – 8.3 pKi 40,84,100
pKi 7.3 – 8.3 [40,84,100]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 7.6 pKi 118
pKi 7.6 [118]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.5 – 7.6 pKi 84
pKi 7.5 – 7.6 [84]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 7.3 pKi 118
pKi 7.3 [118]
UNC9994 Small molecule or natural product Hs Biased agonist 7.1 pKi 3
pKi 7.1 (Ki 7.9x10-8 M) [3]
Description: β-arrestin 2 biased agonist.
compound 3 [PMID: 23134120] Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.9 pKi 119
pKi 6.9 (Ki 1.18x10-7 M) [119]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.8 – 6.9 pKi 84
pKi 6.8 – 6.9 [84]
LP-211 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pKi 70
pKi 6.8 (Ki 1.42x10-7 M) [70]
LP-12 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pKi 69
pKi 6.7 (Ki 2.24x10-7 M) [69]
apomorphine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 5.7 – 7.5 pKi 24,40,84,100,116
pKi 5.7 – 7.5 [24,40,84,100,116]
7-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 – 7.6 pKi 24,40,73
pKi 5.6 – 7.6 [24,40,73]
HS665 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.3 pKi 119
pKi 6.3 (Ki 4.5x10-7 M) [119]
quinpirole Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 – 7.7 pKi 24,83,90,116,118,127
pKi 4.9 – 7.7 [24,83,90,116,118,127]
pramipexole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.1 – 7.4 pKi 83,100
pKi 5.1 – 7.4 [83,100]
7-OH-DPAT Small molecule or natural product Rn Full agonist 6.2 pKi 32
pKi 6.2 [32]
dopamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 4.7 – 7.2 pKi 24,40,100
pKi 4.7 – 7.2 [24,40,100]
PD 128907 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.4 – 6.4 pKi 92,100
pKi 5.4 – 6.4 [92,100]
dopamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 5.3 – 6.4 pKi 102,118
pKi 5.3 – 6.4 [102,118]
7-trans-OH-PIPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 pKi 32
pKi 5.6 [32]
quinelorane Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 – 5.7 pKi 85,116
pKi 5.5 – 5.7 [85,116]
benzquinamide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 5.4 pKi 45
pKi 5.4 (Ki 3.964x10-6 M) [45]
quinpirole Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.2 pKi 118
pKi 5.2 [118]
UNC9975 Small molecule or natural product Hs Biased agonist 9.0 pEC50 3
pEC50 9.0 (EC50 1.1x10-9 M) [3]
Description: This compound shows biased agonism towards D2-mediated β-arrestin-2 translocation measured using the Tango assay.
UNC0006 Small molecule or natural product Hs Biased agonist 8.9 pEC50 3
pEC50 8.9 (EC50 1.2x10-9 M) [3]
Description: Biased agonist of D2-mediated β-arrestin-2 translocation measured using the Tango assay.
UNC9994 Small molecule or natural product Hs Biased agonist 8.2 pEC50 3
pEC50 8.2 (EC50 6.1x10-9 M) [3]
Description: This compound shows biased agonism towards D2-mediated β-arrestin-2 translocation measured using the Tango assay.
aripiprazole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 7.4 pEC50 3
pEC50 7.4 (EC50 3.8x10-8 M) [3]
Description: Measuring cAMP production via the Gi-coupled signaling pathway
vilazodone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.2 pIC50 50
pIC50 6.2 (IC50 6.66x10-7 M) [50]
View species-specific agonist tables
Agonist Comments
Terguride and roxindole have been reported to be partial agonists at the D2S receptor and antagonists at the D2L receptor.
Although benzquinamide has higher affinity for α-adrenoceptors, it is suggested in [45] that it is more likely that drug-induced modulation of D2 receptor activity is responsible for the drug's antiemetic action.
Allosteric modulation of the D2 receptor by SB269652 only occurs when D2 receptor dimers form, with the ligand assuming a 'bitopic' pose and interacting with different sites on each of the two protomers in the dimer [68].
UNC0006, UNC9994 and UNC9975 are partial biased agonists of β-arrestin 2 recruitment at the D2 receptor as measured using three different assays (β-arrestin-2 translocation Tango assay, DiscoveRx assay and BRET-based β-arrestin-2 recruitment assay) [3]. Tango assay pEC50 values and binding Kis are provided in the table above.
G protein-biased, cariprazine-based partial agonists are reported in [113].
Antagonists
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Ligand Sp. Action Value Parameter Reference
[3H]nemonapride Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 10.9 pKd 75
pKd 10.9 [75]
[3H]spiperone Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Antagonist 10.2 pKd 23,51,139
pKd 10.2 (Kd 5.7x10-11 M) [23,51,139]
[3H]raclopride Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 8.9 pKd 65
pKd 8.9 (Kd 1.2x10-9 M) [65]
[3H]N-methylspiperone Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 10.7 pKi 102
pKi 10.7 [102]
benperidol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.6 pKi 109
pKi 10.6 (Ki 2.7x10-11 M) [109]
blonanserin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.9 pKi 88
pKi 9.9 (Ki 1.4x10-10 M) [88]
pipotiazine Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 9.7 pKi 117
pKi 9.7 (Ki 2x10-10 M) [117]
risperidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.4 pKi 10
pKi 9.4 (Ki 4.4x10-10 M) [10]
perphenazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.9 – 9.6 pKi 62,106
pKi 8.9 – 9.6 (Ki 1.4x10-9 – 2.6x10-10 M) [62,106]
perospirone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.2 pKi 107
pKi 9.2 (Ki 6x10-10 M) [107]
eticlopride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.2 pKi 73,123
pKi 9.2 [73,123]
trifluoperazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.9 – 9.0 pKi 62,108
pKi 8.9 – 9.0 (Ki 1.3x10-9 – 9.6x10-10 M) [62,108]
asenapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.9 pKi 112
pKi 8.9 (Ki 1.2x10-9 M) [112]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.9 pKi 84
pKi 8.9 [84]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.4 – 9.4 pKi 73,85,118,123
pKi 8.4 – 9.4 [73,85,118,123]
fluphenazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 pKi 99
pKi 8.8 (Ki 1.44x10-9 M) [99]
flupentixol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 pKi 40
pKi 8.8 (Ki 1.5x10-9 M) [40]
nafadotride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.8 pKi 102
pKi 8.8 [102]
lurasidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.8 pKi 54
pKi 8.8 (Ki 1.68x10-9 M) [54]
olanzapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.7 pKi 10
pKi 8.7 (Ki 2.1x10-9 M) [10]
mesoridazine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.7 pKi 31
pKi 8.7 (Ki 2.2x10-9 M) [31]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 84
pKi 8.6 [84]
ziprasidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.6 pKi 10
pKi 8.6 (Ki 2.8x10-9 M) [10]
chlorprothixene Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 pKi 128
pKi 8.5 (Ki 2.96x10-9 M) [128]
nafadotride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 101
pKi 8.5 [101]
raclopride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.7 – 9.3 pKi 102,118
pKi 7.7 – 9.3 [102,118]
domperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.5 pKi 118
pKi 8.5 [118]
sertindole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.0 – 8.9 pKi 61-62,106
pKi 8.0 – 8.9 (Ki 9.1x10-9 – 1.2x10-9 M) [61-62,106]
prochlorperazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 12
pKi 8.4 (Ki 3.61x10-9 M) [12]
haloperidol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.3 pKi 118
pKi 8.3 [118]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 40
pKi 8.2 (Ki 6x10-9 M) [40]
L-741,626 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.5 pKi 46,64
pKi 7.9 – 8.5 [46,64]
domperidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.9 – 8.4 pKi 40,116
pKi 7.9 – 8.4 (Ki 1.26x10-8 – 3.98x10-9 M) [40,116]
loxapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.9 – 8.3 pKi 62,108
pKi 7.9 – 8.3 (Ki 1.2x10-8 – 5x10-9 M) [62,108]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 8.7 pKi 24,40,73,123
pKi 7.5 – 8.7 [24,40,73,123]
haloperidol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 – 8.8 pKi 40,73,83,116,124
pKi 7.4 – 8.8 [40,73,83,116,124]
raclopride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.0 pKi 85
pKi 8.0 (Ki 1x10-8 M) [85]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.0 pKi 105
pKi 8.0 (Ki 1.1x10-8 M) [105]
(-)-stepholidine Small molecule or natural product Hs Antagonist 7.9 pKi 82
pKi 7.9 (Ki 1.16x10-8 M) [82]
pimozide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 8.8 pKi 40,116
pKi 7.0 – 8.8 [40,116]
amisulpride Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 7.8 – 8.0 pKi 77,116,118
pKi 7.9 – 8.0 [77,116]
pKi 7.8 [118]
pimozide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.6 pKi 118
pKi 7.6 [118]
sulpiride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.2 – 7.9 pKi 24
pKi 7.2 – 7.9 (Ki 6x10-8 – 1.2x10-8 M) [24]
metoclopramide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Mm Antagonist 7.5 pKi 79
pKi 7.5 (Ki 2.88x10-8 M) [79]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.5 pKi 118
pKi 7.5 [118]
lumateperone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.5 pKi 71,115
pKi 7.5 (Ki 3.2x10-8 M) [71,115]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 7.6 pKi 40,116
pKi 7.0 – 7.6 [40,116]
quetiapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.2 pKi 10
pKi 7.2 (Ki 6.9x10-8 M) [10]
(-)-sulpiride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.3 – 8.0 pKi 40,116,123
pKi 6.3 – 8.0 (Ki 5.2x10-7 – 1x10-8 M) [40,116,123]
R-VK4-40 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 56
pKi 7.1 (Ki 7.58x10-8 M) [56]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.0 pKi 118
pKi 7.0 [118]
ML321 Small molecule or natural product Primary target of this compound Hs Antagonist 7.0 pKi 133-134
pKi 7.0 (Ki 1x10-7 M) [133-134]
trans-flupenthixol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 pKi 40
pKi 6.9 (Ki 1.2x10-7 M) [40]
EGIS-11150 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 pKi 41
pKi 6.9 (Ki 1.2x10-7 M) [41]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 – 7.1 pKi 40,118
pKi 6.4 – 7.1 [40,118]
promazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.5 pKi 25
pKi 6.5 (Ki 3x10-7 M) [25]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.4 pKi 118
pKi 6.4 [118]
clozapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 5.8 – 6.9 pKi 40,73,112,116,123
pKi 5.8 – 6.9 [40,73,112,116,123]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 6.2 pKi 118
pKi 6.2 [118]
(+)-S-14297 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 pKi 85
pKi 5.5 [85]
(+)-SCH-23390 Small molecule or natural product Hs Antagonist 5.3 pKi 40
pKi 5.3 [40]
iloperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.0 pIC50 121
pIC50 7.0 (IC50 1.1x10-7 M) [121]
Description: Measuring displacement of [3H]spiperone from rat striatum.
metopimazine Small molecule or natural product Approved drug N/A Antagonist - -
alizapride Small molecule or natural product Approved drug N/A Antagonist - -
View species-specific antagonist tables
Antagonist Comments
Terguride/roxindole have been reported to act as partial agonists at the D2S receptor and as antagonists at the D2L receptor.
Perphenazine is an antagonist at both the D2S and D2L receptors [122].
The approved drug mesoridazine, although consisting of 4 stereoisomers, appears to be selective for the D2 receptor [31], especially when examining the data for the two highest affinity isomers, compounds 2 and 5. Across the 3 dopamine receptors, compounds 2 and 5 have the same order of potency (D2>D3>D1). The data shown in the table above is for compound 2. Mesoridazine is also a selective antagonist of the serotonin 5-HT2A receptor.
Zotepine has a Ki of 5.4nM for the D2S receptor isoform [105].
The β-arrestin biased ligands UNC9975, UNC0006 and UNC9994, do not activate D2 receptor-mediated Gi-regulated inhibition of cAMP production, but rather are functionally-selective antagonists of the interaction between D2 receptor and β-arrestin-2 [3].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SB269652 Small molecule or natural product