Target Validation Information
TTD ID T22118
Target Name Dopamine D1 receptor (D1R)
Type of Target
Successful
Drug Potency against Target Fenoldopam Drug Info Ki = 15.0 nM [40]
Pergolide Drug Info EC50 = 1040 nM [42]
Drug Info Ki = 3410 nM [13]
(+)-(1R,1'S)-berbamunine hydrochloride Drug Info IC50 = 1040 nM
(+)-(1R,1'S)-thaligrisine hydrochloride Drug Info IC50 = 5600 nM
(+)-BUTACLAMOL Drug Info Ki = 1.8 nM [3]
(+/-)-nantenine Drug Info Ki = 895 nM [24]
(-)-(1S,1'R)-O,O-dimethylgrisbine hydrochloride Drug Info IC50 = 5640 nM
(R)-(+)-coclaurine Drug Info IC50 = 240 nM [36]
(R)-(-)-10-methyl-11-hydroxyaporphine Drug Info Ki = 9650 nM [9]
(R)-(-)-11-hydroxy-N-n-propylnoraporphine Drug Info Ki = 699 nM [13]
(R)-(-)-2-methoxy-11-hydroxyaporphine Drug Info Ki = 46 nM [13]
(R)-(-)-2-methoxy-N-npropylnorapomorphine Drug Info Ki = 6450 nM [13]
(R)-(-)-N-ethyl-2-methoxy-11-hydroxynoraporphine Drug Info Ki = 130 nM [13]
(R)-(-)-N-propyl-2-methoxy-11-hydroxynoraporphine Drug Info Ki = 1690 nM [13]
(R)-11-Amino-2-methoxyaporphine Drug Info Ki = 78 nM [16]
(R)-2,11-Diaminoaporphine Drug Info Ki = 2920 nM [16]
(R,S)-homoaromaline hydrochloride Drug Info IC50 = 15400 nM
(S)-BULBOCAPNINE Drug Info IC50 = 740 nM [8]
(S)APOMORPHINE Drug Info Ki = 2980 nM [21]
(S,S)-oxandrine hydrochloride Drug Info IC50 = 11100 nM
1,2,3,7,12,12a-hexahydro-1-aza-pleiaden-5-ol Drug Info Ki = 3700 nM [8]
1,2,3,7,12,12a-hexahydro-1-aza-pleiadene-5,6-diol Drug Info Ki = 10800 nM [8]
1,2-Bis-[R-(-)-apomorphine-2'-oxy]ethane Drug Info Ki = 5200 nM [14]
1-(4-(1H-pyrazol-1-yl)benzyl)-4-phenylpiperazine Drug Info Ki = 7600 nM [7]
1-Aminomethyl-3-cyclohexyl-isochroman-5,6-diol Drug Info Ki = 5.4 nM [15]
1-Aminomethyl-3-phenyl-isochroman-5,6-diol Drug Info Ki = 7200 nM [23]
1-Aminomethyl-isochroman-5,6-diol Drug Info Ki = 1030 nM [23]
1-Benzyl-4-(2-ethynyl-pyrrol-1-yl)-piperidine Drug Info Ki = 14000 nM [1]
1-Benzyl-4-(2-iodo-pyrrol-1-yl)-piperidine Drug Info Ki = 11000 nM [1]
1-Benzyl-4-(2-oxazol-5-yl-pyrrol-1-yl)-piperidine Drug Info Ki = 10000 nM [1]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine Drug Info IC50 = 1500 nM [31]
1-[2-(2-Benzyl-phenoxy)-ethyl]-piperidine Drug Info Ki = 33.7 nM [4]
1-[2-(2-Benzyl-phenoxy)-ethyl]-pyrrolidine Drug Info Ki = 379 nM [4]
1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine Drug Info Ki = 113 nM [4]
11-Butyryloxy-N-n-propylnoraporphine Drug Info Ki = 12 nM [17]
11-Heptanoyloxy-N-n-propylnoraporphine Drug Info Ki = 31 nM [17]
11-Hexanoyloxy-N-n-propylnoraporphine Drug Info Ki = 10 nM [17]
11-Propionyloxy-N-n-propylnoraporphine Drug Info Ki = 18 nM [17]
11-valeryloxynoraporphine Drug Info Ki = 23 nM [17]
2-methoxyapomorphine Drug Info Ki = 2600 nM [14]
2-Methyl-8-phenyl-1,2,3,4-tetrahydro-isoquinoline Drug Info IC50 = 27 nM [33]
2-{[R-(-)-Apomorphine-2'-oxy]ethoxy}-ethanol Drug Info Ki = 7600 nM [14]
3,8-dibromoboldine Drug Info IC50 = 206 nM [2]
3-bromoboldine Drug Info IC50 = 66 nM [2]
3-Chloroboldine Drug Info IC50 = 81 nM [2]
3-Iodoboldine Drug Info IC50 = 3 nM [2]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info Ki < 1000 nM [25]
4-[2-(2-Benzyl-phenoxy)-ethyl]-morpholine Drug Info Ki = 201 nM [4]
6-(2-Amino-ethyl)-biphenyl-2,3,4'-triol Drug Info Ki = 1650 nM [28]
6-(2-Amino-ethyl)-biphenyl-2,3-diol Drug Info Ki = 1500 nM [28]
6-(2-Dipropylamino-ethyl)-biphenyl-2,3,4'-triol Drug Info Ki = 1740 nM [28]
6-(2-Dipropylamino-ethyl)-biphenyl-2,3-diol Drug Info Ki = 1940 nM [28]
9-Aminomethyl-9H-fluorene-2,5,6-triol Drug Info Ki = 43 nM [28]
9-Aminomethyl-9H-fluorene-3,4-diol Drug Info Ki = 380 nM [28]
A-68930 Drug Info Ki = 1.6 nM [23]
BOLDINE Drug Info IC50 = 400 nM [2]
BP-897 Drug Info Ki = 636 nM [5]
Ecopipam Drug Info Ki = 1.9 nM [26]
Etoloxamine Drug Info Ki = 1959 nM [4]
FALCARINDIOL Drug Info Ki = 192 nM [12]
FLUMEZAPINE Drug Info IC50 = 20 nM [30]
FLUTROLINE Drug Info IC50 = 14 nM [29]
GLAUCINE Drug Info Ki = 2900 nM [8]
IBZM Drug Info Ki = 12000 nM [10]
ISOCLOZAPINE Drug Info IC50 = 11 nM [35]
ISOLOXAPINE Drug Info IC50 = 2480 nM [32]
MCL-516 Drug Info Ki = 1480 nM [19]
MELOSMINE Drug Info IC50 = 12500 nM [8]
N-(4-Dipropylaminobutyl)-4-biphenylcarboxamide Drug Info Ki = 6800 nM [18]
N-(4-Propylaminobutyl)-4-biphenylcarboxamide Drug Info Ki = 7300 nM [18]
NORSTEPHALAGINE Drug Info IC50 = 4800 nM [8]
Phenyltoloxamine Drug Info Ki = 343 nM [4]
PUKATEINE Drug Info IC50 = 400 nM [8]
QUINPIROLE Drug Info Ki = 63 nM [6]
Ro-21-7767 Drug Info IC50 = 955 nM [34]
SB-271046 Drug Info Ki = 120 nM [11]
SCH-12679 Drug Info IC50 = 491 nM [38]
SCH-24518 Drug Info Ki = 2.35 nM [27]
SK&F-89626 Drug Info IC50 = 120 nM [20]
STEPHOLIDINE Drug Info Ki = 5.9 nM [22]
TEPA (possesses cytotoxic activity) Drug Info IC50 = 430 nM [37]
[R-(-)-Apomorphine-2-yl]-(2'-hydroxy-ethyl)ether Drug Info Ki = 5300 nM [14]
Action against Disease Model Fenoldopam Drug Info EC50 in relaxation of preconstricted mesenteric/l uMbar/renal artery: 3600nM/6200nM/3400nM [41]
Methylergonovine Drug Info The h uMan histamine H1 receptor (H1R) is an important, well characterized target for the development of antagonists to treat allergic conditions. Many neuropsychiatric drugs are known to potently antagonize the H1R, thereby producing some of their side effects. In contrast, the tolerability and potential therapeutic utility of H1R agonism is currently unclear. We have used a cell-based functional assay to evaluate known therapeutics and reference drugs for H1R agonist activity. Our initial functional screen identified three ergot-based compounds possessing heretofore-unknown H1R agonist activity. 8R-lisuride demonstrated potent agonist activity in various assays including receptor selection and amplification technology, inositol phosphate acc uMulation, and activation of nuclear factor-kappaB with pEC50 values of 8.1, 7.9, and 7.9, respectively, and with varying degrees of efficacy. Based on these assays, 8R-lisuride is the most potent stereospecific partial agonist for the h uMan H1R yet reported. Investigation of the residues involved in histamine and lisuride binding, using H1R mutants and molecular modeling, have revealed that although these ligands are structurally different, the lisuride-binding pocket in the H1R closely corresponds to the histamine-binding pocket. The discovery of a potent stereospecific partial H1R agonist provides a valuable tool to further characterize this important therapeutic target in vitro. [39]
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