|
Inhibition of [3H]raclopride binding to Dopamine receptor D2 of rat striatum membranes
|
Rattus norvegicus
|
228.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects.
Year : 1999
Volume : 9
Issue : 20
First Page : 2999
Last Page : 3002
Authors : Annoura H, Nakanishi K, Uesugi M, Fukunaga A, Miyajima A, Tamura-Horikawa Y, Tamura S.
Abstract : A series of novel arylpiperidines (4a-d) which have highly potent blocking effects for both neuronal Na+ and T-type Ca2+ channels with extremely low affinity for dopamine D2 receptors were synthesized. Among these compounds, 1-(2-hydroxy-3-phenoxy)propyl-4-(4-phenoxyphenyl)-piperidine hydrochloride (4c; SUN N5030) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (MCAO) model.
|
Concentration required for 50% inhibitory effect on Dopamine receptor D2 determined in competition experiments with [3H]raclopride
|
None
|
228.0
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a dual Na(+) and Ca(2+) channel blocker with antioxidant activity.
Year : 2000
Volume : 43
Issue : 18
First Page : 3372
Last Page : 3376
Authors : Annoura H, Nakanishi K, Toba T, Takemoto N, Imajo S, Miyajima A, Tamura-Horikawa Y, Tamura S.
|
Inhibition of veratridine-induced Na+ influx in chinese hamster ovary cells expressing alpha subunit of rat brain type voltage-gated sodium channel type 2
|
Rattus norvegicus
|
420.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers.
Year : 1994
Volume : 37
Issue : 2
First Page : 268
Last Page : 274
Authors : Roufos I, Hays SJ, Dooley DJ, Schwarz RD, Campbell GW, Probert AW.
Abstract : The synthesis and structure-activity relationships of a series of phenylacetamides related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenylbenzeneacetamide (1) (PD85639) acting at the voltage-dependent Na+ channel are described. All structural variations for this study were made in the phenylacetic acid portion of these molecules, and the compounds were synthesized by coupling the appropriately substituted phenylacetic acid derivative with 3-[1-(2,6-dimethyl)piperidinyl]-propanamine using standard methods of amide formation. Compounds were tested as inhibitors of [3H]batrachtoxinin binding in rat neocortical membranes and also as inhibitors of veratridine-induced Na+ influx in Chinese hamster ovary cells expressing type IIA Na+ channels. Diphenylacetic acid derivatives with halogenated aromatic rings (12-15) were very potent in both assays, while alkoxy and alkyl substitution did not affect activity (16 and 17). Selected compounds were tested as potential neuroprotective agents in two cell culture assays involving inhibition of veratridine-induced and hypoxia-induced lactate dehydrogenase release. Compound 15 was equipotent with flunarizine, a reference compound in both neuroprotection assays.
|
Calcium channel-blocking activity by determined by ability to antagonize calcium-induced contractions of isolated rabbit aortic strips
|
Oryctolagus cuniculus
|
5.012
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis, calcium-channel-blocking activity, and antihypertensive activity of 4-(diarylmethyl)-1-[3-(aryloxy)propyl]piperidines and structurally related compounds.
Year : 1991
Volume : 34
Issue : 10
First Page : 3011
Last Page : 3022
Authors : Shanklin JR, Johnson CP, Proakis AG, Barrett RJ.
Abstract : A series of 4-(diarylmethyl)-1-[3-(aryloxy)propyl]piperidines and structurally related compounds were synthesized as calcium-channel blockers and antihypertensive agents. Compounds were evaluated for calcium-channel-blocking activity by determining their ability to antagonize calcium-induced contractions of isolated rabbit aortic strips. The most potent compounds were those with fluoro substituents in the 3- and/or 4-positions of both rings of the diphenylmethyl group. Bis(4-fluorophenyl)acetonitrile analogue 79 was similar in potency to bis(4-fluorophenyl)methyl compound 1. The methylene analogue of 1 (78) and derivatives of 1 that contained a hydroxyl (76), carbamoyl (80), amino (81), or acetamido (82) substituent on the methyl group were less potent. In most cases, substituents on the phenoxy ring, changes in the distance between the aryloxy group and the piperidine nitrogen, and the substitution of S, N(CH3), or CH2 for the oxygen atom of the aryloxy group had only a small to moderate effect on the potency. The best compounds in this series were more potent than verapamil, diltiazem, flunarizine, and lidoflazine, but were less potent than nifedipine. Compounds were evaluated for antihypertensive activity in spontaneously hypertensive rats (SHR) at an oral dose of 30 mg/kg. Of the 55 compounds tested, only nine produced a statistically significant (p less than 0.05) reduction in blood pressure greater than 20%; all of these compounds had fluoro substituents in both rings of the diphenylmethyl group. One of the most active compounds in the SHR at 30 mg/kg was 1-[4-[3-[4-[bis(3,4-difluorophenyl)methyl]-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone (63), which produced a 35% reduction in blood pressure and was similar in activity to nifedipine. At lower doses, however, 4-[bis(4-fluorophenyl)methyl]-1-[3-(4-chlorophenoxy)propyl]piperidine (93) was one of the most effective antihypertensive agents, producing reductions in blood pressure of 17 and 11% at oral doses of 10 and 3 mg/kg, respectively; 63 was inactive at 10 mg/kg.
|
Inhibition of veratridine-induced depolarization in rat cerebrocortical synaptosomes using the voltage sensitive fluorescent dye Rhodamine 6G
|
Rattus norvegicus
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects.
Year : 1999
Volume : 9
Issue : 20
First Page : 2999
Last Page : 3002
Authors : Annoura H, Nakanishi K, Uesugi M, Fukunaga A, Miyajima A, Tamura-Horikawa Y, Tamura S.
Abstract : A series of novel arylpiperidines (4a-d) which have highly potent blocking effects for both neuronal Na+ and T-type Ca2+ channels with extremely low affinity for dopamine D2 receptors were synthesized. Among these compounds, 1-(2-hydroxy-3-phenoxy)propyl-4-(4-phenoxyphenyl)-piperidine hydrochloride (4c; SUN N5030) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (MCAO) model.
|
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
|
Cavia porcellus
|
600.0
nM
|
|
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.
|
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
|
96.7
%
|
|
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.
|
Inhibition of [3H]- batrachotoxin binding to sodium channel in rat neocortical membrane
|
Rattus norvegicus
|
53.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers.
Year : 1994
Volume : 37
Issue : 2
First Page : 268
Last Page : 274
Authors : Roufos I, Hays SJ, Dooley DJ, Schwarz RD, Campbell GW, Probert AW.
Abstract : The synthesis and structure-activity relationships of a series of phenylacetamides related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenylbenzeneacetamide (1) (PD85639) acting at the voltage-dependent Na+ channel are described. All structural variations for this study were made in the phenylacetic acid portion of these molecules, and the compounds were synthesized by coupling the appropriately substituted phenylacetic acid derivative with 3-[1-(2,6-dimethyl)piperidinyl]-propanamine using standard methods of amide formation. Compounds were tested as inhibitors of [3H]batrachtoxinin binding in rat neocortical membranes and also as inhibitors of veratridine-induced Na+ influx in Chinese hamster ovary cells expressing type IIA Na+ channels. Diphenylacetic acid derivatives with halogenated aromatic rings (12-15) were very potent in both assays, while alkoxy and alkyl substitution did not affect activity (16 and 17). Selected compounds were tested as potential neuroprotective agents in two cell culture assays involving inhibition of veratridine-induced and hypoxia-induced lactate dehydrogenase release. Compound 15 was equipotent with flunarizine, a reference compound in both neuroprotection assays.
|
Inhibitory activity against type IIA sodium channel in CNaIIA-1 cell line expressed in CHO cells
|
None
|
490.0
nM
|
|
Journal : J. Med. Chem.
Title : A structure-activity relationship study of novel phenylacetamides which are sodium channel blockers.
Year : 1996
Volume : 39
Issue : 7
First Page : 1514
Last Page : 1520
Authors : Roufos I, Hays S, Schwarz RD.
Abstract : A structure-activity relationship study of a series of novel Na(+) channel blockers, structurally related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenylbenzeneacetamide (1, PD85639) is described. The diphenylacetic acid portion of the molecule was left unchanged throughout the study, while structural features in the amine portion and the amide alkyl linkage of the molecule were modified. The compounds were tested for inhibition of veratridine-stimulated Na(+) influx in CHO cells expressing type IIA Na(+) channels. Several derivatives show a trend toward more potent Na+ channel blockade activity with increasing lipophilicity of the amine portion of the molecule. The presence of a phenyl ring near the amine increases inhibitory potency. A three-carbon spacer between the amide and amine is optimal, and a secondary amide linkage is preferred.
|
Inhibition of [3H]BTX binding to cardiac voltage-gated sodium channel
|
Rattus norvegicus
|
350.0
nM
|
|
Journal : J. Med. Chem.
Title : Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Year : 2001
Volume : 44
Issue : 2
First Page : 115
Last Page : 137
Authors : Anger T, Madge DJ, Mulla M, Riddall D.
|
Inhibition of veratridine-induced guanidine flux in cardiac voltage-gated sodium channel (veratridine block vs. Na release)
|
Rattus norvegicus
|
120.0
nM
|
|
Journal : J. Med. Chem.
Title : Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Year : 2001
Volume : 44
Issue : 2
First Page : 115
Last Page : 137
Authors : Anger T, Madge DJ, Mulla M, Riddall D.
|
Inhibitory concentration against KCl induced rat thoracic aorta contraction
|
Rattus norvegicus
|
270.0
nM
|
|
Journal : J. Med. Chem.
Title : A novel series of 2,6,7-substituted 2,3-dihydro-1,4-benzodioxin and 2,6,7-substituted 1,4-benzodioxin derivatives as lipid peroxidation inhibitors. Structure-activity relationships for high inhibition of human low-density lipoprotein peroxidation.
Year : 2001
Volume : 44
Issue : 23
First Page : 3904
Last Page : 3914
Authors : Thiéry V, Coudert G, Bizot-Espiard JG, Pfeiffer B, Renard P, Lindenbaum A, Guillaumet G.
Abstract : A series of 6- or 7-substituted 2-carboxamido- or 2-(aminomethyl)-1,4-benzodioxin and -2,3-dihydro-1,4-benzodioxin derivatives were synthesized and evaluated to determine the necessary structural requirements for a high inhibition of human low-density lipoprotein copper-induced peroxidation. The most active compounds (21, 25, 28, 36, and 37) were found between 5 and >45 times more active than probucol itself. Due to both their potency and their structural features, compounds 25 and 36 were selected with others for complementary in vitro and in vivo investigations. Both of them exhibit calcium antagonist properties in the same range of potency as flunarizine itself. Compound 36 was also found to have significant hypolipaemic activity in mice at 100 and 300 mg/kg po, while compound 25 proved to be clearly active in a normobar hypoxia test.
|
Inhibition of veratridine-induced depolarization of rat cerebrocortical synaptosomes using a membrane potential sensitive fluorescent dye, rhodamine 6G
|
Rattus norvegicus
|
290.0
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a dual Na(+) and Ca(2+) channel blocker with antioxidant activity.
Year : 2000
Volume : 43
Issue : 18
First Page : 3372
Last Page : 3376
Authors : Annoura H, Nakanishi K, Toba T, Takemoto N, Imajo S, Miyajima A, Tamura-Horikawa Y, Tamura S.
|
Inhibition of calcium channel L type in IMR32 cells
|
Homo sapiens
|
780.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers.
Year : 2007
Volume : 17
Issue : 3
First Page : 662
Last Page : 667
Authors : Knutsen LJ, Hobbs CJ, Earnshaw CG, Fiumana A, Gilbert J, Mellor SL, Radford F, Smith NJ, Birch PJ, Russell Burley J, Ward SD, James IF.
Abstract : A series of new N-type (Ca(v)2.2) calcium channel blockers derived from the 'hit' structures 2-(3-bromo-4-fluorophenyl)-3-(2-pyridin-2-ylethyl)thiazolidin-4-one 9 and its 2-[4-(4-bromophenyl)pyridin-3-yl]-3-isobutyl analogue 10 is described. Extensive SAR studies using a range of synthetic approaches resulted in novel, patented compounds with IC50 values of up to 0.2 microM in an in vitro IMR32 assay, and selectivities for N/L of up to 30-fold. The new compounds described have potential in treatment of neuropathic pain.
|
Blocking of rat N-type calcium channel alpha-1B/alpha-2-delta-1/beta-1b activity expressed in HEK293 cells assessed as whole cell current by whole cell patch clamp assay
|
Rattus norvegicus
|
80.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Scaffold-based design and synthesis of potent N-type calcium channel blockers.
Year : 2009
Volume : 19
Issue : 22
First Page : 6467
Last Page : 6472
Authors : Zamponi GW, Feng ZP, Zhang L, Pajouhesh H, Ding Y, Belardetti F, Pajouhesh H, Dolphin D, Mitscher LA, Snutch TP.
Abstract : The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel.
|
Blocking of rat Voltage-dependent L-type calcium channel alpha1c/alpha2delta-1/beta1b activity expressed in HEK293 cells assessed as whole cell current by whole cell patch clamp assay
|
Rattus norvegicus
|
310.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Scaffold-based design and synthesis of potent N-type calcium channel blockers.
Year : 2009
Volume : 19
Issue : 22
First Page : 6467
Last Page : 6472
Authors : Zamponi GW, Feng ZP, Zhang L, Pajouhesh H, Ding Y, Belardetti F, Pajouhesh H, Dolphin D, Mitscher LA, Snutch TP.
Abstract : The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel.
|
Inhibition of T-type Cav3.1 channel
|
None
|
530.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and T-type calcium channel blocking activity of novel diphenylpiperazine compounds, and evaluation of in vivo analgesic activity.
Year : 2010
Volume : 18
Issue : 16
First Page : 5938
Last Page : 5944
Authors : Kam YL, Rhee HK, Rhim H, Back SK, Na HS, Choo HY.
Abstract : Novel diphenylpiperazine derivatives were synthesized and evaluated for their inhibitory activity against T-type calcium channel by whole-cell patch clamp recordings on HEK293 cells. Among the test compounds, 2 and 3d were effective in decreasing the response to formalin in both the first and second phases and demonstrated antiallodynic effects in a rat model of neuropathic pain.
|
Inhibition of T-type Cav3.3 channel
|
None
|
840.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and T-type calcium channel blocking activity of novel diphenylpiperazine compounds, and evaluation of in vivo analgesic activity.
Year : 2010
Volume : 18
Issue : 16
First Page : 5938
Last Page : 5944
Authors : Kam YL, Rhee HK, Rhim H, Back SK, Na HS, Choo HY.
Abstract : Novel diphenylpiperazine derivatives were synthesized and evaluated for their inhibitory activity against T-type calcium channel by whole-cell patch clamp recordings on HEK293 cells. Among the test compounds, 2 and 3d were effective in decreasing the response to formalin in both the first and second phases and demonstrated antiallodynic effects in a rat model of neuropathic pain.
|
Binding affinity to T-type alpha1G calcium channel
|
None
|
530.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Facile synthesis and biological evaluation of 3,3-diphenylpropanoyl piperazines as T-type calcium channel blockers.
Year : 2011
Volume : 21
Issue : 1
First Page : 215
Last Page : 219
Authors : Choi YH, Baek du J, Seo SH, Lee JK, Pae AN, Cho YS, Min SJ.
Abstract : We have developed a facile synthesis of 3,3-diphenylpropanamides using Meldrum's acid derivatives as amide coupling components. The in vitro biological evaluation of the title compounds led to the identification of compound 1h, which has good inhibitory activity against T-type calcium channel (IC(50) = 0.83 μM).
|
Binding affinity to T-type alpha1I calcium channel
|
None
|
840.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Facile synthesis and biological evaluation of 3,3-diphenylpropanoyl piperazines as T-type calcium channel blockers.
Year : 2011
Volume : 21
Issue : 1
First Page : 215
Last Page : 219
Authors : Choi YH, Baek du J, Seo SH, Lee JK, Pae AN, Cho YS, Min SJ.
Abstract : We have developed a facile synthesis of 3,3-diphenylpropanamides using Meldrum's acid derivatives as amide coupling components. The in vitro biological evaluation of the title compounds led to the identification of compound 1h, which has good inhibitory activity against T-type calcium channel (IC(50) = 0.83 μM).
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
707.0
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
|
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: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
789.0
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
|
795.0
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: Potassium Channel HERG radioligand binding (ligand: [3H] Astemizole)
|
None
|
605.8
nM
|
|
DRUGMATRIX: Potassium Channel HERG radioligand binding (ligand: [3H] Astemizole)
|
None
|
496.3
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
|
407.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
116.0
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
|
440.0
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
|
606.0
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
|
533.0
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
|
581.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
218.0
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
|
864.0
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
|
222.0
nM
|
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
32.0
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
|
995.0
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, Dihydropyridine radioligand binding (ligand: [3H] Nitrendipine)
|
Rattus norvegicus
|
650.0
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
|
692.0
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
|
669.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
351.0
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
|
499.0
nM
|
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
265.0
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: Sigma1 radioligand binding (ligand: [3H] Haloperidol)
|
None
|
25.0
nM
|
|
DRUGMATRIX: Sigma1 radioligand binding (ligand: [3H] Haloperidol)
|
None
|
10.0
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: Sigma2 radioligand binding (ligand: [3H] Ifenprodil)
|
Rattus norvegicus
|
62.0
nM
|
|
DRUGMATRIX: Sigma2 radioligand binding (ligand: [3H] Ifenprodil)
|
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: Sodium Channel, Site 2 radioligand binding (ligand: [3H] Batrachotoxin)
|
Rattus norvegicus
|
263.0
nM
|
|
DRUGMATRIX: Sodium Channel, Site 2 radioligand binding (ligand: [3H] Batrachotoxin)
|
Rattus norvegicus
|
240.0
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
|
177.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
172.0
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
|
352.0
nM
|
|
DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
117.0
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
|
97.0
nM
|
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
33.0
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 Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
584.0
nM
|
|
DRUGMATRIX: Dopamine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
464.0
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
|
158.0
nM
|
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
18.0
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
|
Non-competitive inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-demethylation by LC-MS/MS method and Dixon plot
|
Homo sapiens
|
100.0
nM
|
|
Journal : Drug Metab. Dispos.
Title : Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
Year : 2013
Volume : 41
Issue : 1
First Page : 60
Last Page : 71
Authors : Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L.
Abstract : Cytochrome P450 (CYP) 2J2 is one of the human CYPs involved in phase I xenobiotics metabolism. It is mainly expressed in extrahepatic tissues, including intestine and cardiovascular systems. The general role of CYP2J2 in drug metabolism is not yet fully understood, and the recent discovery that CYP2J2 can metabolize a wide range of structurally diverse drugs and its primary distribution in the intestine suggest its potentially indispensable role in first-pass intestinal metabolism and involvement in drug-drug interaction. To fully characterize its role in drug metabolism, selective and potent inhibitors of CYP2J2 are necessary tools. In the current study, 69 known drugs were screened for the inhibition of CYP2J2, and we discovered a number of marketed drugs as potent and selective CYP2J2 inhibitors. In particular, telmisartan and flunarizine have CYP2J2 inhibition IC(50) values of 0.42 μM and 0.94 μM, respectively, which are at least 10-fold more selective against all other major metabolizing CYPs; moreover, they are not substrates of CYP2J2 and show no time-dependent inhibition toward this CYP. The results of enzyme kinetics studies, supported by molecular modeling, have also elucidated that telmisartan is a mixed-type inhibitor, and flunarizine competitively inhibits CYP2J2. The K(i) for telmisartan is 0.19 μM, with an α value, an indicator of the type of inhibition mechanism, of 2.80, and flunarizine has a K(i) value of 0.13 μM. These newly discovered CYP2J2 inhibitors can be potentially used as a tool to study CYP2J2 in drug metabolism and interaction in a clinical setting.
|
Inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-demethylation by LC-MS/MS method
|
Homo sapiens
|
940.0
nM
|
|
Journal : Drug Metab. Dispos.
Title : Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
Year : 2013
Volume : 41
Issue : 1
First Page : 60
Last Page : 71
Authors : Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L.
Abstract : Cytochrome P450 (CYP) 2J2 is one of the human CYPs involved in phase I xenobiotics metabolism. It is mainly expressed in extrahepatic tissues, including intestine and cardiovascular systems. The general role of CYP2J2 in drug metabolism is not yet fully understood, and the recent discovery that CYP2J2 can metabolize a wide range of structurally diverse drugs and its primary distribution in the intestine suggest its potentially indispensable role in first-pass intestinal metabolism and involvement in drug-drug interaction. To fully characterize its role in drug metabolism, selective and potent inhibitors of CYP2J2 are necessary tools. In the current study, 69 known drugs were screened for the inhibition of CYP2J2, and we discovered a number of marketed drugs as potent and selective CYP2J2 inhibitors. In particular, telmisartan and flunarizine have CYP2J2 inhibition IC(50) values of 0.42 μM and 0.94 μM, respectively, which are at least 10-fold more selective against all other major metabolizing CYPs; moreover, they are not substrates of CYP2J2 and show no time-dependent inhibition toward this CYP. The results of enzyme kinetics studies, supported by molecular modeling, have also elucidated that telmisartan is a mixed-type inhibitor, and flunarizine competitively inhibits CYP2J2. The K(i) for telmisartan is 0.19 μM, with an α value, an indicator of the type of inhibition mechanism, of 2.80, and flunarizine has a K(i) value of 0.13 μM. These newly discovered CYP2J2 inhibitors can be potentially used as a tool to study CYP2J2 in drug metabolism and interaction in a clinical setting.
|
Inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-demethylation reduction in astemizole O-demethylation after 30 mins by LC-MS/MS method in absence of 1 mM NADPH
|
Homo sapiens
|
950.0
nM
|
|
Journal : Drug Metab. Dispos.
Title : Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
Year : 2013
Volume : 41
Issue : 1
First Page : 60
Last Page : 71
Authors : Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L.
Abstract : Cytochrome P450 (CYP) 2J2 is one of the human CYPs involved in phase I xenobiotics metabolism. It is mainly expressed in extrahepatic tissues, including intestine and cardiovascular systems. The general role of CYP2J2 in drug metabolism is not yet fully understood, and the recent discovery that CYP2J2 can metabolize a wide range of structurally diverse drugs and its primary distribution in the intestine suggest its potentially indispensable role in first-pass intestinal metabolism and involvement in drug-drug interaction. To fully characterize its role in drug metabolism, selective and potent inhibitors of CYP2J2 are necessary tools. In the current study, 69 known drugs were screened for the inhibition of CYP2J2, and we discovered a number of marketed drugs as potent and selective CYP2J2 inhibitors. In particular, telmisartan and flunarizine have CYP2J2 inhibition IC(50) values of 0.42 μM and 0.94 μM, respectively, which are at least 10-fold more selective against all other major metabolizing CYPs; moreover, they are not substrates of CYP2J2 and show no time-dependent inhibition toward this CYP. The results of enzyme kinetics studies, supported by molecular modeling, have also elucidated that telmisartan is a mixed-type inhibitor, and flunarizine competitively inhibits CYP2J2. The K(i) for telmisartan is 0.19 μM, with an α value, an indicator of the type of inhibition mechanism, of 2.80, and flunarizine has a K(i) value of 0.13 μM. These newly discovered CYP2J2 inhibitors can be potentially used as a tool to study CYP2J2 in drug metabolism and interaction in a clinical setting.
|
Inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-demethylation after 30 mins by LC-MS/MS method in presence of 1 mM NADPH
|
Homo sapiens
|
760.0
nM
|
|
Journal : Drug Metab. Dispos.
Title : Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
Year : 2013
Volume : 41
Issue : 1
First Page : 60
Last Page : 71
Authors : Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L.
Abstract : Cytochrome P450 (CYP) 2J2 is one of the human CYPs involved in phase I xenobiotics metabolism. It is mainly expressed in extrahepatic tissues, including intestine and cardiovascular systems. The general role of CYP2J2 in drug metabolism is not yet fully understood, and the recent discovery that CYP2J2 can metabolize a wide range of structurally diverse drugs and its primary distribution in the intestine suggest its potentially indispensable role in first-pass intestinal metabolism and involvement in drug-drug interaction. To fully characterize its role in drug metabolism, selective and potent inhibitors of CYP2J2 are necessary tools. In the current study, 69 known drugs were screened for the inhibition of CYP2J2, and we discovered a number of marketed drugs as potent and selective CYP2J2 inhibitors. In particular, telmisartan and flunarizine have CYP2J2 inhibition IC(50) values of 0.42 μM and 0.94 μM, respectively, which are at least 10-fold more selective against all other major metabolizing CYPs; moreover, they are not substrates of CYP2J2 and show no time-dependent inhibition toward this CYP. The results of enzyme kinetics studies, supported by molecular modeling, have also elucidated that telmisartan is a mixed-type inhibitor, and flunarizine competitively inhibits CYP2J2. The K(i) for telmisartan is 0.19 μM, with an α value, an indicator of the type of inhibition mechanism, of 2.80, and flunarizine has a K(i) value of 0.13 μM. These newly discovered CYP2J2 inhibitors can be potentially used as a tool to study CYP2J2 in drug metabolism and interaction in a clinical setting.
|
Non-competitive inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-demethylation by LC-MS/MS method
|
Homo sapiens
|
130.0
nM
|
|
Journal : Drug Metab. Dispos.
Title : Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
Year : 2013
Volume : 41
Issue : 1
First Page : 60
Last Page : 71
Authors : Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L.
Abstract : Cytochrome P450 (CYP) 2J2 is one of the human CYPs involved in phase I xenobiotics metabolism. It is mainly expressed in extrahepatic tissues, including intestine and cardiovascular systems. The general role of CYP2J2 in drug metabolism is not yet fully understood, and the recent discovery that CYP2J2 can metabolize a wide range of structurally diverse drugs and its primary distribution in the intestine suggest its potentially indispensable role in first-pass intestinal metabolism and involvement in drug-drug interaction. To fully characterize its role in drug metabolism, selective and potent inhibitors of CYP2J2 are necessary tools. In the current study, 69 known drugs were screened for the inhibition of CYP2J2, and we discovered a number of marketed drugs as potent and selective CYP2J2 inhibitors. In particular, telmisartan and flunarizine have CYP2J2 inhibition IC(50) values of 0.42 μM and 0.94 μM, respectively, which are at least 10-fold more selective against all other major metabolizing CYPs; moreover, they are not substrates of CYP2J2 and show no time-dependent inhibition toward this CYP. The results of enzyme kinetics studies, supported by molecular modeling, have also elucidated that telmisartan is a mixed-type inhibitor, and flunarizine competitively inhibits CYP2J2. The K(i) for telmisartan is 0.19 μM, with an α value, an indicator of the type of inhibition mechanism, of 2.80, and flunarizine has a K(i) value of 0.13 μM. These newly discovered CYP2J2 inhibitors can be potentially used as a tool to study CYP2J2 in drug metabolism and interaction in a clinical setting.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
16.91
%
|
|
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
|
3.22
%
|
|
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
|
3.22
%
|
|
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.
