|
Compound was tested for its inhibitory activity against 5-hydroxytryptamine receptor
|
Rattus norvegicus
|
170.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound was tested for its binding affinity towards brain (Hippocampus) Adenylate cyclase
|
Cavia porcellus
|
450.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound was tested for its binding affinity towards brain (neocortex) Adenylate cyclase
|
Cavia porcellus
|
280.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound was tested for its inhibitory activity against Alpha-1 adrenergic receptor
|
None
|
0.04
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound tested for its inhibitory activity against Histamine H1 receptor
|
None
|
0.05
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
In vitro inhibition of the accumulation of (-)-[3H]Norepinephrine in slices from the middle part of the mouse brain.
|
Mus musculus
|
500.0
nM
|
|
Journal : J. Med. Chem.
Title : Homoallylic amines related to zimeldine. A comparative study on neuronal serotonin and norepinephrine reuptake based on conformational analysis.
Year : 1988
Volume : 31
Issue : 5
First Page : 913
Last Page : 919
Authors : Högberg T, Ross SB, Ström P, Grunewald GL, Creese MW, Bunce JD.
Abstract : A number of tertiary and secondary homoallylic amines, i.e. (Z)- and (E)-4-(4-bromophenyl)-4-(3-pyridyl)-3-buten-1-ylamines, were synthesized in diastereomerically pure forms. The compounds were evaluated as neuronal norepinephrine (NE) and serotonin (5-HT) uptake inhibitors under in vitro and ex vivo conditions and compared with the tricyclics amitriptyline and nortriptyline having homoallylic side chains and with the corresponding diastereomers in the zimeldine series having allylic side chains. The Z isomers of the new homoallylic derivatives (3Z, 4Z) were specific 5-HT uptake inhibitors in analogy with the corresponding allylic derivatives zimeldine (1Z) and norzimeldine (2Z). Likewise, the selectivity profile of the homoallylic (3E, 4E) and the allylic (1E, 2E) derivatives was comparable. In general, the homoallylic compounds were less potent inhibitors than their allylic counterparts. The similarities and discrepancies were evaluated in terms of conformational preferences determined by CAMSEQ molecular mechanics calculations. Homonorzimeldine (4Z) can accommodate energetically favored, but less populated, conformations having amino nitrogen atom to aromatic ring center distances comparable to those in norzimeldine. These facts correlate to retained 5-HT selectivity but diminished potency of 4Z compared to 2Z.
|
Compound was evaluated for its binding affinity towards human NET (norepinephrine) transporter
|
None
|
6.3
nM
|
|
Journal : J. Med. Chem.
Title : 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.
Year : 2000
Volume : 43
Issue : 5
First Page : 1011
Last Page : 1018
Authors : Glennon RA, Lee M, Rangisetty JB, Dukat M, Roth BL, Savage JE, McBride A, Rauser L, Hufeisen S, Lee DK.
Abstract : Several 2-alkyl-5-methoxytryptamine analogues were designed and prepared as potential 5-HT(6) serotonin agonists. It was found that 5-HT(6) receptors accommodate small alkyl substituents at the indole 2-position and that the resulting compounds can bind with affinities comparable to that of serotonin. In particular, 2-ethyl-5-methoxy-N, N-dimethyltryptamine (8) binds with high affinity at human 5-HT(6) receptors (K(i) = 16 nM) relative to 5-HT (K(i) = 75 nM) and was a full agonist, at least as potent (8: K(act) = 3.6 nM) as serotonin (K(act) = 5.0 nM), in activating adenylate cyclase. Compound 8 displays modest affinity for several other populations of 5-HT receptors, notably h5-HT(1A) (K(i) = 170 nM), h5-HT(1D) (K(i) = 290 nM), and h5-HT(7) (K(i) = 300 nM) receptors, but is otherwise quite selective. Compound 8 represents the first and most selective 5-HT(6) agonist reported to date. Replacing the 2-ethyl substituent with a phenyl group results in a compound that retains 5-HT(6) receptor affinity (i.e., 10: K(i) = 20 nM) but lacks agonist character. 2-Substituted tryptamines, then, might allow entry to a novel class of 5-HT(6) agonists and antagonists.
|
Compound was tested for its inhibitory activity against Noradrenaline receptor
|
Rattus norvegicus
|
9.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
In vitro inhibition of the accumulation of (-)-[3H]Norepinephrine in synaptosomes from the rat brain cortex
|
Rattus norvegicus
|
7.0
nM
|
|
Journal : J. Med. Chem.
Title : Homoallylic amines related to zimeldine. A comparative study on neuronal serotonin and norepinephrine reuptake based on conformational analysis.
Year : 1988
Volume : 31
Issue : 5
First Page : 913
Last Page : 919
Authors : Högberg T, Ross SB, Ström P, Grunewald GL, Creese MW, Bunce JD.
Abstract : A number of tertiary and secondary homoallylic amines, i.e. (Z)- and (E)-4-(4-bromophenyl)-4-(3-pyridyl)-3-buten-1-ylamines, were synthesized in diastereomerically pure forms. The compounds were evaluated as neuronal norepinephrine (NE) and serotonin (5-HT) uptake inhibitors under in vitro and ex vivo conditions and compared with the tricyclics amitriptyline and nortriptyline having homoallylic side chains and with the corresponding diastereomers in the zimeldine series having allylic side chains. The Z isomers of the new homoallylic derivatives (3Z, 4Z) were specific 5-HT uptake inhibitors in analogy with the corresponding allylic derivatives zimeldine (1Z) and norzimeldine (2Z). Likewise, the selectivity profile of the homoallylic (3E, 4E) and the allylic (1E, 2E) derivatives was comparable. In general, the homoallylic compounds were less potent inhibitors than their allylic counterparts. The similarities and discrepancies were evaluated in terms of conformational preferences determined by CAMSEQ molecular mechanics calculations. Homonorzimeldine (4Z) can accommodate energetically favored, but less populated, conformations having amino nitrogen atom to aromatic ring center distances comparable to those in norzimeldine. These facts correlate to retained 5-HT selectivity but diminished potency of 4Z compared to 2Z.
|
Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 10 uM
|
Cavia porcellus
|
69.4
%
|
|
Journal : J. Med. Chem.
Title : [3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
Year : 1985
Volume : 28
Issue : 3
First Page : 381
Last Page : 388
Authors : McNeal ET, Lewandowski GA, Daly JW, Creveling CR.
Abstract : [3H]Batrachotoxinin A benzoate ( [3H]BTX-B) binds with high affinity to sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex. In this preparation, local anesthetics competitively antagonize the binding of [3H]BTX-B. The potencies of some 40 classical local anesthetics and a variety of catecholamine, histamine, serotonin, adenosine, GABA, glycine, acetylcholine, and calcium antagonists, tranquilizers, antidepressants, barbiturates, anticonvulsants, steroids, vasodilators, antiinflammatories, anticoagulants, analgesics, and other agents have been determined. An excellent correlation with the known local anesthetic activity of many of these agents indicate that antagonism of binding of [3H]BTX-B binding provides a rapid, quantitative, and facile method for the screening and investigation of local anesthetic activity.
|
Percent Inhibition of trypanothione reductase activity at 28.5 uM concentration
|
Trypanosoma cruzi
|
0.0
%
|
|
Journal : J. Med. Chem.
Title : A virtual screening approach applied to the search for trypanothione reductase inhibitors.
Year : 1997
Volume : 40
Issue : 15
First Page : 2412
Last Page : 2423
Authors : Horvath D.
Abstract : A prediction algorithm of the binding affinity of ligands to trypanothione reductase (TR), the enzyme replacing glutathione reductase in the metabolism of trypanosomatidae, has been used for the "virtual screening" of a data base of 2500 molecular sketches and has detected several structures of putative TR ligands. Most of these compounds turned out to be micromolar inhibitors of TR, as predicted by the algorithm. While their inhibitory potencies are lower than those of previously reported compounds, one of the molecules reported here could represent the lead toward a structurally different class of TR inhibitors. The fully automated prediction algorithm converts the 2D molecular sketches into 3D ligand structures, explores the conformational space of the latter, and performs a grid-based, rigid-body docking of the resulting family of ligand conformations into the TR site, calculating enthalpic and entropic binding indexes and predicting the binding affinity. The docking model has also been used to obtain hints about the binding modes of TR ligands.
|
Percent Inhibition of trypanothione reductase activity at 5.7 uM concentration
|
Trypanosoma cruzi
|
0.0
%
|
|
Journal : J. Med. Chem.
Title : A virtual screening approach applied to the search for trypanothione reductase inhibitors.
Year : 1997
Volume : 40
Issue : 15
First Page : 2412
Last Page : 2423
Authors : Horvath D.
Abstract : A prediction algorithm of the binding affinity of ligands to trypanothione reductase (TR), the enzyme replacing glutathione reductase in the metabolism of trypanosomatidae, has been used for the "virtual screening" of a data base of 2500 molecular sketches and has detected several structures of putative TR ligands. Most of these compounds turned out to be micromolar inhibitors of TR, as predicted by the algorithm. While their inhibitory potencies are lower than those of previously reported compounds, one of the molecules reported here could represent the lead toward a structurally different class of TR inhibitors. The fully automated prediction algorithm converts the 2D molecular sketches into 3D ligand structures, explores the conformational space of the latter, and performs a grid-based, rigid-body docking of the resulting family of ligand conformations into the TR site, calculating enthalpic and entropic binding indexes and predicting the binding affinity. The docking model has also been used to obtain hints about the binding modes of TR ligands.
|
Percent Inhibition of trypanothione reductase activity at 57 uM concentration
|
Trypanosoma cruzi
|
25.0
%
|
|
Journal : J. Med. Chem.
Title : A virtual screening approach applied to the search for trypanothione reductase inhibitors.
Year : 1997
Volume : 40
Issue : 15
First Page : 2412
Last Page : 2423
Authors : Horvath D.
Abstract : A prediction algorithm of the binding affinity of ligands to trypanothione reductase (TR), the enzyme replacing glutathione reductase in the metabolism of trypanosomatidae, has been used for the "virtual screening" of a data base of 2500 molecular sketches and has detected several structures of putative TR ligands. Most of these compounds turned out to be micromolar inhibitors of TR, as predicted by the algorithm. While their inhibitory potencies are lower than those of previously reported compounds, one of the molecules reported here could represent the lead toward a structurally different class of TR inhibitors. The fully automated prediction algorithm converts the 2D molecular sketches into 3D ligand structures, explores the conformational space of the latter, and performs a grid-based, rigid-body docking of the resulting family of ligand conformations into the TR site, calculating enthalpic and entropic binding indexes and predicting the binding affinity. The docking model has also been used to obtain hints about the binding modes of TR ligands.
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
82.0
nM
|
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
20.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
347.0
nM
|
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
123.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
171.0
nM
|
|
DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
36.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
95.0
nM
|
|
DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
13.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
27.0
nM
|
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
20.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
51.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
15.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
305.0
nM
|
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
123.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
207.0
nM
|
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
114.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
273.0
nM
|
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
134.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
732.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
275.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
94.0
nM
|
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
43.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
203.0
nM
|
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
30.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
3.21
nM
|
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
3.184
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
136.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
86.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
16.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
8.169
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
554.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
257.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
13.0
nM
|
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
6.977
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
539.0
nM
|
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
269.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
179.0
nM
|
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
61.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
50.0
nM
|
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
5.862
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cells after 1.5 hrs by liquid scintillation counting
|
Homo sapiens
|
214.0
nM
|
|
Journal : J. Med. Chem.
Title : Chemocentric informatics approach to drug discovery: identification and experimental validation of selective estrogen receptor modulators as ligands of 5-hydroxytryptamine-6 receptors and as potential cognition enhancers.
Year : 2012
Volume : 55
Issue : 12
First Page : 5704
Last Page : 5719
Authors : Hajjo R, Setola V, Roth BL, Tropsha A.
Abstract : We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure-Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5-HT(6)R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT(6)R actives. Second, we queried chemogenomics data from the Connectivity Map ( http://www.broad.mit.edu/cmap/ ) with the gene expression profile signatures of Alzheimer's disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT(6)R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT(6)R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations.
|
DNDI: Malaria in Vitro, 72 hour
|
Plasmodium falciparum
|
580.0
nM
|
|
Title : Antiprotozoal Activity Profiling of Approved Drugs: A Starting Point toward Drug Repositioning
Authors : Kaiser M, Mäser P, Tadoori LP, Ioset JR, Brun R.
Abstract : In this study, a set of 100 registered drugs with drug repositioning potential for neglected tropical diseases was assembled. The compound collection was systematically screened against protozoan parasites, namely T. b. rhodesiense, L. donovani, T. cruzi and P. falciparum. Several drugs and drug classes exhibited in vitro activity and selectivity against one of the protozoan parasites. The results offer opportunities for drug repurposing and the identified compound classes could also be a starting point for new drug discovery projects. See also publication: Antiprotozoal Activity Profiling of Approved Drugs: A Starting Point toward Drug Repositioning. PLoS One. 2015 10(8): e0135556.
|
Antiplasmodial activity against Plasmodium falciparum K1 at 0.002 to 100 ug/ml by serial drug dilution assay
|
Plasmodium falciparum K1
|
500.0
nM
|
|
Journal : Bioorg Med Chem
Title : Astemizole analogues with reduced hERG inhibition as potent antimalarial compounds.
Year : 2017
Volume : 25
Issue : 24
First Page : 6332
Last Page : 6344
Authors : Tian J, Vandermosten L, Peigneur S, Moreels L, Rozenski J, Tytgat J, Herdewijn P, Van den Steen PE, De Jonghe S.
Abstract : Astemizole is a H1-antagonist endowed with antimalarial activity, but has hERG liabilities. Systematic structural modifications of astemizole led to the discovery of analogues that display very potent activity as inhibitors of the growth of the Plasmodium parasite, but show a decreased hERG inhibition, when compared to astemizole. These compounds can be used as starting point for the development of a new class of antimalarials.
