|
Binding affinity towards alpha-2 adrenergic receptor in rat using [3H]rauwolscine as radioligand
|
None
|
30.0
nM
|
|
Journal : J. Med. Chem.
Title : Conformationally defined adrenergic agents. 1. Design and synthesis of novel alpha 2 selective adrenergic agents: electrostatic repulsion based conformational prototypes.
Year : 1985
Volume : 28
Issue : 10
First Page : 1398
Last Page : 1404
Authors : DeBernardis JF, Kerkman DJ, Winn M, Bush EN, Arendsen DL, McClellan WJ, Kyncl JJ, Basha FZ.
Abstract : A previous report of the adrenergic selectivity of 2- and 6-fluoronorepinephrine prompted us to formulate a hypothesis that accounted for this selectivity on the basis of a conformational preference induced by electrostatic repulsion between the aromatic fluorine atom and the side-chain hydroxyl group. A series of nitrogen-substituted catechol (aminomethyl)benzocyclobutenes, indanes, tetralins, and benzocycloheptenes were prepared, and when their radioligand binding affinities were determined, it was found that the overall pattern of binding affinity results supported the electrostatic repulsion hypothesis. The radioligand binding assay also revealed several highly alpha 2 selective adrenergic agents among these compounds, with the binding selectivity maximizing for compounds having nitrogen substituted with a group no larger than methyl and having a five-membered carbocyclic ring (i.e., 16, 17, and 19).
|
Binding affinity against alpha-1 adrenergic receptor in rat using [3H]prazosin as radioligand
|
None
|
740.0
nM
|
|
Journal : J. Med. Chem.
Title : Conformationally defined adrenergic agents. 1. Design and synthesis of novel alpha 2 selective adrenergic agents: electrostatic repulsion based conformational prototypes.
Year : 1985
Volume : 28
Issue : 10
First Page : 1398
Last Page : 1404
Authors : DeBernardis JF, Kerkman DJ, Winn M, Bush EN, Arendsen DL, McClellan WJ, Kyncl JJ, Basha FZ.
Abstract : A previous report of the adrenergic selectivity of 2- and 6-fluoronorepinephrine prompted us to formulate a hypothesis that accounted for this selectivity on the basis of a conformational preference induced by electrostatic repulsion between the aromatic fluorine atom and the side-chain hydroxyl group. A series of nitrogen-substituted catechol (aminomethyl)benzocyclobutenes, indanes, tetralins, and benzocycloheptenes were prepared, and when their radioligand binding affinities were determined, it was found that the overall pattern of binding affinity results supported the electrostatic repulsion hypothesis. The radioligand binding assay also revealed several highly alpha 2 selective adrenergic agents among these compounds, with the binding selectivity maximizing for compounds having nitrogen substituted with a group no larger than methyl and having a five-membered carbocyclic ring (i.e., 16, 17, and 19).
|
Binding affinity for human Alpha-1D adrenergic receptor from cultured LM(tk-) cells using [3H]- prazosin
|
Homo sapiens
|
933.25
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Effective concentration at Alpha-2A adrenergic receptor from CHO-C10 cells
|
None
|
4.1
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Year : 1997
Volume : 40
Issue : 1
First Page : 18
Last Page : 23
Authors : Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME.
Abstract : A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
|
Displacement of rauwolscine from human Alpha-2A adrenergic receptor expressed in CHO cells
|
Homo sapiens
|
2.7
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Year : 1997
Volume : 40
Issue : 1
First Page : 18
Last Page : 23
Authors : Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME.
Abstract : A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
|
Alpha-2A adrenergic receptor agonistic potency as inhibition of forskolin-stimulated synthesis of cyclic adenosine monophosphate
|
Homo sapiens
|
0.6166
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Binding affinity for human Alpha-2A adrenergic receptor from cultured LM(tk-) cells using [3H]rauwolscine
|
Homo sapiens
|
6.761
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Binding affinity for Alpha-2 adrenergic receptor of CHO-C10 membrane preparation
|
Cricetulus griseus
|
2.4
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Analogs of UK 14,304: Structural features responsible for 2 adrenoceptor activity
Year : 1995
Volume : 5
Issue : 15
First Page : 1745
Last Page : 1750
Authors : Munk S, Harcourt D, Arasasingham P, Gluchowski C, Wong H, Burke J, Kharlamb A, Manlapaz C, Padillo E, Williams L, Wheeler L, Garst M
|
Inhibition of [3H]p-aminoclonidine (PAC) binding to alpha-2 adrenergic receptor of purified human platelet plasma membranes
|
None
|
3.0
nM
|
|
Journal : J. Med. Chem.
Title : Radioiodinated p-iodoclonidine: a high-affinity probe for the alpha 2-adrenergic receptor.
Year : 1987
Volume : 30
Issue : 7
First Page : 1241
Last Page : 1244
Authors : Van Dort M, Neubig R, Counsell RE.
Abstract : The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding assays conducted with purified human platelet plasma membrane fractions. For the synthesis of radioiodinated PIC the triazene intermediate 11 was synthesized from 2,6-dichloro-4-nitroaniline in five synthetic steps. Acid-catalyzed decomposition of 11 with no-carrier-added Na125I afforded high specific activity [125I]PIC. In view of its high affinity for the alpha 2-adrenergic receptor, [125I]PIC is a potentially useful probe for studies in adrenergic pharmacology.
|
Binding affinity towards Alpha-2 adrenergic receptor of HT-29 cells
|
None
|
2.4
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Analogs of UK 14,304 as 2-adrenoceptor agonists. Twist and agent polarity as design elements.
Year : 1994
Volume : 4
Issue : 3
First Page : 459
Last Page : 462
Authors : Munk S, Gluchowski C, Dolby L, Wong H, Burke J, Kharlamb A, Manlapaz C, Padillo E, Rodgers D, Ohta B, Wheeler L, Garst M
|
Alpha-2B adrenergic receptor agonistic potency as inhibition of forskolin-stimulated cyclic adenosine monophosphate synthesis
|
Homo sapiens
|
281.84
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Binding affinity for human Alpha-2B adrenergic receptor from cultured Y-1 cells using [3H]rauwolscine
|
Homo sapiens
|
34.67
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Effective Concentration at Alpha-2B adrenergic receptor from CHO-RNG cells
|
None
|
55.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Year : 1997
Volume : 40
Issue : 1
First Page : 18
Last Page : 23
Authors : Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME.
Abstract : A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
|
Displacement of rauwolscine from rat Alpha-2B adrenergic receptor expressed in CHO cells
|
Capnocytophaga
|
52.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Year : 1997
Volume : 40
Issue : 1
First Page : 18
Last Page : 23
Authors : Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME.
Abstract : A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
|
Effective concentration at Alpha-2C adrenergic receptor from CHO-C4 cells
|
None
|
3.4
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Year : 1997
Volume : 40
Issue : 1
First Page : 18
Last Page : 23
Authors : Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME.
Abstract : A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
|
Displacement of rauwolscine from human Alpha-2C adrenergic receptor expressed in CHO cells
|
Homo sapiens
|
44.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Year : 1997
Volume : 40
Issue : 1
First Page : 18
Last Page : 23
Authors : Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME.
Abstract : A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.
|
Inhibition of Alpha-2 adrenergic receptor induced contractile response of rabbit vas deferens
|
Oryctolagus cuniculus
|
1.0
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Analogs of UK 14,304: Structural features responsible for 2 adrenoceptor activity
Year : 1995
Volume : 5
Issue : 15
First Page : 1745
Last Page : 1750
Authors : Munk S, Harcourt D, Arasasingham P, Gluchowski C, Wong H, Burke J, Kharlamb A, Manlapaz C, Padillo E, Williams L, Wheeler L, Garst M
|
Alpha-2C adrenergic receptor agonistic potency as inhibition of forskolin-stimulated cyclic adenosine monophosphate synthesis
|
Homo sapiens
|
9.55
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Binding affinity for human Alpha-2C adrenergic receptor from cultured LM(tk-) cells using [3H]- prazosin
|
Homo sapiens
|
83.18
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacological evaluation of UK-14,304 analogs at cloned human adrenergic receptors
Year : 1995
Volume : 5
Issue : 19
First Page : 2255
Last Page : 2258
Authors : Jeon YT, Luo C, Forray C, Vaysse PJ, Branchek TA, Gluchowski C
|
Binding affinity against Alpha-2 adrenergic receptor is the ability to inhibit the specific [3H]clonidine binding (0.4 nM) to rat isolated brain membranes by 50% was reported; 3.6*10e-9
|
None
|
3.6
nM
|
|
Journal : J. Med. Chem.
Title : Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists.
Year : 1984
Volume : 27
Issue : 4
First Page : 495
Last Page : 503
Authors : Timmermans PB, de Jonge A, Thoolen MJ, Wilffert B, Batink H, van Zwieten PA.
Abstract : Quantitative relationships between in vitro affinity for alpha 1- and alpha 2-adrenoceptors (specific binding sites in rat brain membranes of [3H]prazosin and [3H]clonidine, respectively) and in vitro and in vivo alpha 1/alpha 2-adrenoceptor agonist/antagonist activities were derived for a series of 11 alpha-adrenergic antagonists and 35 agonists of dissimilar chemical structure. For the antagonists, the alpha 1/alpha 2-binding selectivity ratio most significantly correlated with the functional alpha 1/alpha 2-blocking selectivity ratios assessed in vitro (rabbit isolated pulmonary artery: antagonism of alpha 1-adrenoceptor-induced vasoconstriction and alpha 2-adrenoceptor-evoked facilitation of transmitter release) and in vivo (antagonism of alpha 1- and alpha 2-adrenoceptor-mediated vasoconstriction in pithed normotensive rats). These results show that the in vitro alpha 1- and alpha 2-adrenoceptor binding affinities of the antagonists provide adequate information concerning their functional alpha 1- and alpha 2-adrenoceptor blocking potencies against agonists. For the agonists, the central, alpha 2-adrenoceptor-elicited, hypotensive activity was not correlated with alpha 1-adrenoceptor binding affinity but was most significantly described in terms of affinity for alpha 2-adrenoceptors and a parabolic dependence on log P' (octanol/buffer; pH 7.4; 37 degrees C). The relevance of log P' in the regression is explained by the difference in accessibility to the membrane-bound alpha 2-adrenoceptors in the radioligand displacement experiments and the central medullary (hypotensive) alpha 2-adrenoceptors in the intact animal. In contrast, the affinity parameters for alpha 1- and alpha 2-adrenoceptors were found to be poor descriptors of the hypertensive potency of the agonists in which alpha 1- and alpha 2-adrenoceptors are known to play a role. The correlations in which the individual binding parameters and the combination of both variables were included reached only a moderate significance level.(ABSTRACT TRUNCATED AT 250 WORDS)
|
Ability to inhibit contractile response of an electrically stimulated rabbit vas deferens
|
Oryctolagus cuniculus
|
1.0
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Analogs of UK 14,304 as 2-adrenoceptor agonists. Twist and agent polarity as design elements.
Year : 1994
Volume : 4
Issue : 3
First Page : 459
Last Page : 462
Authors : Munk S, Gluchowski C, Dolby L, Wong H, Burke J, Kharlamb A, Manlapaz C, Padillo E, Rodgers D, Ohta B, Wheeler L, Garst M
|
Maximum percent inhibition electrically evoked contractions of rat vas deferens by the compound was determined as test for its agonistic activity
|
Rattus norvegicus
|
100.0
%
|
|
Journal : J. Med. Chem.
Title : Heteroaromatic analogues of the alpha 2-adrenoreceptor partial agonist clonidine.
Year : 1989
Volume : 32
Issue : 7
First Page : 1627
Last Page : 1630
Authors : Chapleo CB, Butler RC, England DC, Myers PL, Roach AG, Smith CF, Stillings MR, Tulloch IF.
Abstract : A 1,4-dioxane analogue (1) of the alpha 2-adrenoreceptor partial agonist clonidine (2) has previously been shown to possess an interesting but complex pharmacological profile. In this study, from a series of other heterocyclic analogues of clonidine, the 1,4-oxazines 6 and 12 were found to resemble 1 in that they are partial alpha 2-agonists in the periphery and are excluded from the central nervous system. However, when given directly into the brain, they behave as pure alpha 2-antagonists.
|
Binding affinity to alpha2 adrenoceptor in human cortical membrane
|
Homo sapiens
|
1.413
nM
|
|
Journal : J. Med. Chem.
Title : Guanidine and 2-aminoimidazoline aromatic derivatives as alpha2-adrenoceptor ligands: searching for structure-activity relationships.
Year : 2009
Volume : 52
Issue : 3
First Page : 601
Last Page : 609
Authors : Rodriguez F, Rozas I, Ortega JE, Erdozain AM, Meana JJ, Callado LF, Callado LF.
Abstract : In this paper, we report the synthesis of three new 2-aminoimidazoline (compounds 4b, 5b, and 6b) and three new guanidine derivatives (compounds 7b, 8b, and 9b) as potential alpha(2)-adrenoceptor antagonists for the treatment of depression. Their pharmacological profile was evaluated in vitro in human brain tissue and compared to the potential antidepressant 1 and the agonists 2 and 3. All new substrates were evaluated by in vitro functional [(35)S]GTPgammaS binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Compound 8b was found to be an antagonist in vitro and was subjected to in vivo microdialysis experiments in rats. Moreover, a new synthesis of the precursor amines for compounds 4b-9b is presented.
|
Displacement of [3H]RX821002 from alpha2 adrenergic receptor in human brain prefrontal cortex tissue by liquid scintillation spectrometry
|
Homo sapiens
|
1.413
nM
|
|
Journal : J. Med. Chem.
Title : Guanidine and 2-aminoimidazoline aromatic derivatives as alpha2-adrenoceptor antagonists. 2. Exploring alkyl linkers for new antidepressants.
Year : 2008
Volume : 51
Issue : 11
First Page : 3304
Last Page : 3312
Authors : Rodriguez F, Rozas I, Ortega JE, Erdozain AM, Meana JJ, Callado LF, Callado LF.
Abstract : The preparation of a number of (bis)guanidine and (bis)2-aminoimidazoline derivatives as potential alpha 2-adrenoceptor antagonists for the treatment of depression is presented. Human brain tissue was used to measure their affinity toward the alpha 2-adrenoceptors in vitro. Compounds 6b, 8b, 9b, 10b, 15b, 17b, 18b, 20b, and 21b displayed a good affinity (pKi > 7) and were evaluated in in vitro functional [(35)S]GTPgammaS binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Among these compounds, 17b and 20b showed the expected behavior for an antagonist and were subject to in vivo microdialysis experiments in rats. Significantly, these experiments confirmed the antagonistic properties of 17b and 20b, and therefore both compounds can be considered as potential antidepressants.
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
846.0
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
|
298.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
112.0
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
|
478.0
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: Imidazoline I2, Central radioligand binding (ligand: [3H] Idazoxan)
|
Rattus norvegicus
|
74.0
nM
|
|
DRUGMATRIX: Imidazoline I2, Central radioligand binding (ligand: [3H] Idazoxan)
|
Rattus norvegicus
|
49.0
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
|
Agonist activity at human recombinant alpha-2A receptor expressed in PC12 cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation measured after 10 mins by cAMP enzyme immunoassay
|
Homo sapiens
|
0.86
nM
|
|
Title : Novel methods for identifying improved, non-sedating alpha-2 agonists
Year : 2005
|
Agonist activity at human recombinant alpha-2C receptor expressed in PC12 cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation measured after 10 mins by cAMP enzyme immunoassay
|
Homo sapiens
|
8.0
nM
|
|
Title : Novel methods for identifying improved, non-sedating alpha-2 agonists
Year : 2005
|
Agonist activity at hamster recombinant alpha-1B receptor expressed in HEK293 cells coexpressing Gag-pol assessed as increase in intracellular calcium measured after 60 mins by fluo-4 dye based FLIPR assay
|
Cricetinae
|
943.0
nM
|
|
Title : Novel methods for identifying improved, non-sedating alpha-2 agonists
Year : 2005
|
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
7.02
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
-2.73
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
7.83
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
1.87
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
22.06
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
3.99
%
|
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
-1.44
%
|
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
-13.71
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
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Inhibition of His-tagged human recombinant SHMT2 expressed in Escherichia coli BLR(DE3) assessed as reduction in NADPH level using L-serine, THF and NADP+ at 6.5 or 26.5 uM incubated for 5 mins by SHMT2-MTHFD coupled reaction based fluorescence assay relative to control
|
Homo sapiens
|
79.0
%
|
|
Title : Compositions and methods relating to inhibiting serine hyrdoxymethyltransferase 2 activity
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SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
8.37
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
13.03
%
|
|
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.
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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
|
0.18
%
|
|
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
|
-0.25
%
|
|
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
|
-0.25
%
|
|
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
|
0.18
%
|
|
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.
