|
Evaluated for binding affinity towards rat cortical membranes at 5-hydroxytryptamine 1 receptor binding site by using [3H]-5-HT as a radioligand.
|
None
|
20.0
nM
|
|
Journal : J. Med. Chem.
Title : Central serotonin receptors as targets for drug research.
Year : 1987
Volume : 30
Issue : 1
First Page : 1
Last Page : 12
Authors : Glennon RA.
|
Inhibition of [3H]- OH-DPAT binding against 5-hydroxytryptamine 1A receptor from human recombinant
|
None
|
13.0
nM
|
|
Journal : J. Med. Chem.
Title : A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: discovery of a potential atypical antipsychotic agent.
Year : 1999
Volume : 42
Issue : 25
First Page : 5181
Last Page : 5187
Authors : Belliotti TR, Wustrow DJ, Brink WA, Zoski KT, Shih YH, Whetzel SZ, Georgic LM, Corbin AE, Akunne HC, Heffner TG, Pugsley TA, Wise LD.
Abstract : As part of a program to develop dopamine D4 antagonists for the treatment of schizophrenia, we discovered a series of 6- and 7-(phenylpiperazinyl)- and -(phenylpiperidinyl)methylbenzoxazinones through mass screening of our compound library. A structure-activity relationship SAR study was carried out involving substituents on the phenyl ring, and several selective D4 antagonists were identified. The 7-substituted benzoxazinones showed more activity in neurochemical and behavioral tests than the 6-substituted series. One of the most potent and selective compounds (26) was found to have potent activity in animal tests predictive of antipsychotic activity in humans after oral administration. This paper describes the SAR of the benzoxazinone series and the preclinical characterization of 26.
|
Evaluated for the binding affinity to hippocampus striatal membranes at 5-hydroxytryptamine 1A receptor binding site by using [3H]-8-OH- DPAT as a radioligand.
|
None
|
6.0
nM
|
|
Journal : J. Med. Chem.
Title : Central serotonin receptors as targets for drug research.
Year : 1987
Volume : 30
Issue : 1
First Page : 1
Last Page : 12
Authors : Glennon RA.
|
Binding affinity (Ki) to rat cortical membranes at 5-HT1B binding site by using [125 I] ICYP as a radioligand.
|
None
|
25.0
nM
|
|
Journal : J. Med. Chem.
Title : Central serotonin receptors as targets for drug research.
Year : 1987
Volume : 30
Issue : 1
First Page : 1
Last Page : 12
Authors : Glennon RA.
|
Evaluated for the binding affinity to porcine choroid plexus at 5-hydroxytryptamine 2C receptor binding site by using [3H]-MES as a radioligand.
|
Sus scrofa
|
0.5
nM
|
|
Journal : J. Med. Chem.
Title : Central serotonin receptors as targets for drug research.
Year : 1987
Volume : 30
Issue : 1
First Page : 1
Last Page : 12
Authors : Glennon RA.
|
Binding affinity to rat cortical membranes at 5-hydroxytryptamine 2 (5-HT2) receptor using [3H]KET as a radioligand
|
None
|
0.3
nM
|
|
Journal : J. Med. Chem.
Title : Central serotonin receptors as targets for drug research.
Year : 1987
Volume : 30
Issue : 1
First Page : 1
Last Page : 12
Authors : Glennon RA.
|
Binding affinity to 5-hydroxytryptamine 2 receptor in rat frontal cortical membranes by [3H]- KET displacement.
|
None
|
1.0
nM
|
|
Journal : J. Med. Chem.
Title : Central serotonin receptors as targets for drug research.
Year : 1987
Volume : 30
Issue : 1
First Page : 1
Last Page : 12
Authors : Glennon RA.
|
Binding affinity towards 5-hydroxytryptamine 7 receptor
|
None
|
6.31
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : First pharmacophoric hypothesis for 5-HT7 antagonism.
Year : 2000
Volume : 10
Issue : 10
First Page : 1097
Last Page : 1100
Authors : López-Rodríguez ML, Porras E, Benhamú B, Ramos JA, Morcillo MJ, Lavandera JL.
Abstract : In order to make the first contribution to the elucidation of essential structural features for 5-HT7 antagonism, a set of thirty 5-HT7 antagonists were selected from the literature. A pharmacophore model was built using Molecular Modeling studies with Catalyst program. The information contained in this model was validated with new synthesized compounds.
|
Non-selective inhibitory activity was determined against 5-hydroxytryptamine 7 receptor
|
None
|
6.31
nM
|
|
Journal : J. Med. Chem.
Title : Optimization of the pharmacophore model for 5-HT7R antagonism. Design and synthesis of new naphtholactam and naphthosultam derivatives.
Year : 2003
Volume : 46
Issue : 26
First Page : 5638
Last Page : 5650
Authors : López-Rodríguez ML, Porras E, Morcillo MJ, Benhamú B, Soto LJ, Lavandera JL, Ramos JA, Olivella M, Campillo M, Pardo L.
Abstract : We present in this study an optimization of a preliminary pharmacophore model for 5-HT(7)R antagonism, with the incorporation of recently reported ligands and using an efficient procedure with the CATALYST program. The model consists of five features: a positive ionizable atom (PI), a H-bonding acceptor group (HBA), and three hydrophobic regions (HYD). This model has been supported by the design, synthesis, and biological evaluation of new naphtholactam and naphthosultam derivatives of general structure I (39-72). A systematic structure-affinity relationship (SAFIR) study on these analogues has allowed us to confirm that the model incorporates the essential structural features for 5-HT(7)R antagonism. In addition, computational simulation of the complex between compound 56 and a rhodopsin-based 3D model of the 5-HT(7)R transmembrane domain has permitted us to define the molecular details of the ligand-receptor interaction and gives additional support to the proposed pharmacophore model for 5-HT(7)R antagonism: (i) the HBA feature of the pharmacophore model binds Ser(5.42) and Thr(5.43), (ii) the HYD1 feature interacts with Phe(6.52), (iii) the PI feature forms an ionic interaction with Asp(3.32), and (iv) the HYD3 (AR) feature interacts with a set of aromatic residues (Phe(3.28), Tyr(7.43)). These results provide the tools for the design and synthesis of new ligands with predetermined affinities and pharmacological properties.
|
Displacement of [3H]8-OH-DPAT from human recombinant 5HT1A receptor expressed in CHO cells
|
Homo sapiens
|
7.5
nM
|
|
Journal : J. Nat. Prod.
Title : Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro.
Year : 2006
Volume : 69
Issue : 3
First Page : 432
Last Page : 435
Authors : Gafner S, Dietz BM, McPhail KL, Scott IM, Glinski JA, Russell FE, McCollom MM, Budzinski JW, Foster BC, Bergeron C, Rhyu MR, Bolton JL.
Abstract : A 70% ethanol extract of California poppy (Eschscholzia californica) was able to bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation procedure yielded the known alkaloids californidine (1), escholtzine (2), N-methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The structure of 7 was determined by spectroscopic data interpretation, while the absolute stereochemistry was determined by means of circular dichroism. From the results obtained from the radioligand-binding assay of the pure compounds, including the commercially available protopine (6), it was evident that the activity on the 5-HT(1A) receptor was at least partly due to the presence of the aporphine alkaloid 3, which showed the highest inhibition of [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) binding with an EC(50) value of 155 nM and a K(i) of 85 nM.
|
Inhibition of human FAAH at 1 uM
|
Homo sapiens
|
5.48
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.
Year : 2009
Volume : 19
Issue : 23
First Page : 6793
Last Page : 6796
Authors : Vincent F, Nguyen MT, Emerling DE, Kelly MG, Duncton MA.
Abstract : The screening of known medicinal agents against new biological targets has been shown to be a valuable approach for revealing new pharmacology of marketed compounds. Recently, carbamate, urea and ketone inhibitors of fatty acid amide hydrolase (FAAH) have been described as promising treatments for pain, anxiety, depression and other CNS-related conditions. In order to find novel FAAH inhibitors, a focused screen of molecules containing potentially reactive moieties or having in vivo effects that are possibly relevant to the biology of FAAH was conducted. These studies revealed phenmedipham 13 and amperozide 14 to be inhibitors of human FAAH, with an IC(50) of 377 nM and 1.34 microM, respectively.
|
Displacement of [3H]5CT from 5HT7 receptor
|
None
|
6.31
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : The development and validation of a novel virtual screening cascade protocol to identify potential serotonin 5-HT(7)R antagonists.
Year : 2010
Volume : 20
Issue : 8
First Page : 2465
Last Page : 2468
Authors : Kurczab R, Nowak M, Chilmonczyk Z, Sylte I, Bojarski AJ.
Abstract : In an attempt to identify new ligands for the 5-HT(7) receptor (5-HT(7)R), we developed and tested a hierarchical multi-step strategy of virtual screening (VS) based on two-dimensional (2D) pharmacophore similarity, physicochemical scalar descriptors, an ADME/Tox filter, three-dimensional (3D) pharmacophore searches and a docking protocol. Six chemical classes of 5-HT(7)R antagonists were used as query structures in a double-path virtual screening scheme. The Enamine screening database, consisting of approximately 730,000 commercially available drug-like compounds, was adopted and used as a source of structures. A biological evaluation of 26 finally selected virtual hits resulted in finding two benzodioxane derivatives with significant affinity (K(i)=197 and 265 nM). The approach described in this case study can be easily used as a general rational drug design tool for other biological targets.
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: [3H] 8-OH-DPAT)
|
None
|
6.175
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: [3H] 8-OH-DPAT)
|
None
|
3.528
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-HT1B radioligand binding (ligand: [125I] Cyanopindolol)
|
Rattus norvegicus
|
19.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1B radioligand binding (ligand: [125I] Cyanopindolol)
|
Rattus norvegicus
|
11.0
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
|
0.395
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
0.113
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
|
95.0
nM
|
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
38.0
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
|
262.0
nM
|
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
145.0
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
|
136.0
nM
|
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
67.0
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
|
58.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
22.0
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
|
16.0
nM
|
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
7.516
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
|
189.0
nM
|
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
27.0
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
|
366.0
nM
|
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
363.0
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: Calcium Channel Type L, Benzothiazepine radioligand binding (ligand: [3H] Diltiazem)
|
Rattus norvegicus
|
268.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Benzothiazepine radioligand binding (ligand: [3H] Diltiazem)
|
Rattus norvegicus
|
238.0
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-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
0.442
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
0.281
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
|
0.663
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
0.347
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-HT4 radioligand binding (ligand: [3H] GR-113808)
|
Cavia porcellus
|
274.0
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-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
28.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
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: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
590.0
nM
|
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
313.0
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: Sodium Channel, Site 2 radioligand binding (ligand: [3H] Batrachotoxin)
|
Rattus norvegicus
|
792.0
nM
|
|
DRUGMATRIX: Sodium Channel, Site 2 radioligand binding (ligand: [3H] Batrachotoxin)
|
Rattus norvegicus
|
723.0
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: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
278.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
270.0
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: CYP450, 2D6 enzyme inhibition (substrate: 3-Cyano-7-ethoxycoumarin)
|
None
|
200.0
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 D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
74.0
nM
|
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
37.0
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 D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
63.0
nM
|
|
DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
21.0
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
|
7.689
nM
|
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
2.611
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 Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
63.0
nM
|
|
DRUGMATRIX: Dopamine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
50.0
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
|
480.0
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 H2 radioligand binding (ligand: [125I] Aminopotentidine)
|
None
|
975.0
nM
|
|
DRUGMATRIX: Histamine H2 radioligand binding (ligand: [125I] Aminopotentidine)
|
None
|
959.0
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
|
TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: ? uM, Metergoline: 100 uM) in MDR1-expressing MDCKII cells
|
None
|
84.4
%
|
|
Journal : J. Pharmacol. Exp. Ther.
Title : Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs.
Year : 2002
Volume : 303
Issue : 1
First Page : 1029
Last Page : 1037
Authors : Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW.
Abstract : Membrane permeability and P-glycoprotein (Pgp) can be limiting factors for blood-brain barrier penetration. The objectives of this study were to determine whether there are differences in the in vitro permeability, Pgp substrate profiles, and physicochemical properties of drugs for central nervous system (CNS) and non-CNS indications, and whether these differences are useful criteria in selecting compounds for drug development. Apparent permeability (P(app)) and Pgp substrate profiles for 93 CNS (n = 48) and non-CNS (n = 45) drugs were determined by monolayer efflux. Calcein-AM inhibition assays were used to supplement the efflux results. The CNS set (2 of 48, 4.2%) had a 7-fold lower incidence of passive permeability values <150 nm/s compared with the non-CNS set (13 of 45, 28.9%). The majority of drugs (72.0%, 67 of 93) were not Pgp substrates; however, 49.5% (46 of 93) were positive in the calcein-AM assay when tested at 100 microM. The CNS drug set (n = 7 of 48, 14.6%) had a 3-fold lower incidence of Pgp-mediated efflux than the non-CNS drug set (n = 19 of 45, 42.2%). Analysis of 18 physicochemical properties revealed that the CNS drug set had fewer hydrogen bond donors, fewer positive charges, greater lipophilicity, lower polar surface area, and reduced flexibility compared with the non-CNS group (p < 0.05), properties that enhance membrane permeability. This study on a large, diverse set of marketed compounds clearly demonstrates that permeability, Pgp-mediated efflux, and certain physicochemical properties are factors that differentiate CNS and non-CNS drugs. For CNS delivery, a drug should ideally have an in vitro passive permeability >150 nm/s and not be a good (B --> A/A --> B ratio <2.5) Pgp substrate.
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Displacement of [3H]8-OH-DPAT from human recombinant 5HT1A receptor expressed in CHOK1 cells after 60 mins
|
Homo sapiens
|
2.3
nM
|
|
Displacement of [3H]8-OH-DPAT from human recombinant 5HT1A receptor expressed in CHOK1 cells after 60 mins
|
Homo sapiens
|
4.1
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.
Year : 2013
Volume : 23
Issue : 6
First Page : 1834
Last Page : 1838
Authors : Germain AR, Carmody LC, Nag PP, Morgan B, Verplank L, Fernandez C, Donckele E, Feng Y, Perez JR, Dandapani S, Palmer M, Lander ES, Gupta PB, Schreiber SL, Munoz B.
Abstract : A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure-activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations.
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Displacement of [3H]8-OH-DPAT from human recombinant 5HT1A receptor expressed in CHOK1 cells at 10 uM after 60 mins relative to control
|
Homo sapiens
|
-8.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.
Year : 2013
Volume : 23
Issue : 6
First Page : 1834
Last Page : 1838
Authors : Germain AR, Carmody LC, Nag PP, Morgan B, Verplank L, Fernandez C, Donckele E, Feng Y, Perez JR, Dandapani S, Palmer M, Lander ES, Gupta PB, Schreiber SL, Munoz B.
Abstract : A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure-activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations.
|
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
93.79
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Displacement of [3H]5-HT from recombinant human 5-HT7 receptor expressed in African green monkey COS7 cells
|
Homo sapiens
|
6.31
nM
|
|
Journal : Eur J Med Chem
Title : Structure-activity relationships of serotonin 5-HT<sub>7</sub> receptors ligands: A review.
Year : 2019
Volume : 183
First Page : 111705
Last Page : 111705
Authors : Thirumaran SL, Lepailleur A, Rochais C.
Abstract : 5-HT<sub>7</sub> receptors are the most recently discovered serotonergic receptors, for which numerous physiological implications in the central and the peripheral nervous systems as well as the endocrine system are described. A current public health challenge is to propose new and more efficient treatments against neuropsychiatric disorders such as epilepsy or Alzheimer's disease. In this context, 5-HT<sub>7</sub> receptors represent an interesting target for the treatment and prevention of those pathologies, as an alternative or in association with other medicines. Thus, numerous chemical series of agonists and antagonists have been developed. Some of these molecules have shown a therapeutic potential in various in vivo studies. This review aims to present an overview of 5-HT<sub>7</sub> receptors and of the medicinal chemistry programs that led to the identification of new, potent and selective 5-HT<sub>7</sub> receptors ligands. Structure-activity relationships studies based on molecular docking and pharmacophoric approaches are also described.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
11.48
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
1.52
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
1.52
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
