Page last updated: 2024-11-04

clofilium

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

clofilium: RN given refers to parent cpd; structure [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID2798
CHEMBL ID9484
CHEBI ID34649
SCHEMBL ID157537
MeSH IDM0079394

Synonyms (36)

Synonym
smr001233522
MLS002154263 ,
BPBIO1_000350
PRESTWICK2_000319
BSPBIO_000318
PRESTWICK3_000319
68379-02-2
clofilium
SPBIO_002537
PRESTWICK1_000319
NCGC00168464-02
NCGC00168464-01
4-chloro-n,n-diethyl-n-heptylbenzenebutanaminium
benzenebutanaminium, 4-chloro-n,n-diethyl-n-heptyl-
gtpl2507
4-(4-chlorophenyl)butyl-diethyl-heptylazanium
CHEMBL9484 ,
clofilium cation
clofilium ion
chebi:34649 ,
gnf-pf-3889 ,
AC1L1EHQ ,
unii-847g178bmc
847g178bmc ,
(4-(p-chlorophenyl)butyl)diethylheptylammonium
benzenebutanaminium, 4-chloro-n,n-diethyl-n-heptyl
SCHEMBL157537
DTXSID9048568
bdbm89440
cid_175533
4-(4-chlorophenyl)butyl-diethyl-heptylazanium;4-methylbenzenesulfonate
4-(4-chlorophenyl)butyl-diethyl-heptyl-ammonium;tosylate
4-(4-chlorophenyl)butyl-diethyl-heptylammonium;4-methylbenzenesulfonate
4-(4-chlorophenyl)butyl-diethyl-heptyl-azanium;4-methylbenzenesulfonate
4-(4-chlorophenyl)butyl-diethyl-heptyl-ammonium
Q5134881

Research Excerpts

Overview

Clofilium is an antiarrhythmic agent with a supposedly predominant class-III action. It should be useful in interrupting or suppressing reentrant arrhythmias.

ExcerptReferenceRelevance
"Clofilium is a model for an antiarrhythmic drug which should be useful in interrupting or suppressing reentrant arrhythmias because it increases refractoriness without major changes in conduction time."( Prolongation of cardiac refractory times in man by clofilium phosphate, a new antiarrhythmic agent.
Cobb, LA; Greene, HL; Gross, BW; Sears, GK; Trobaugh, GB; Werner, JA, 1983
)
1.24
"Clofilium is an antiarrhythmic agent with a supposedly predominant class-III action which is related to impairment of K+ channel function. "( Selectivity of class-III antiarrhythmic action of clofilium in guinea pig ventricular myocytes.
Himmel, HM; Li, Q; Ravens, U, 1996
)
1.99

Actions

Clofilium was found to inhibit nimodipine binding with an inhibition constant of approximately 5 microM, whereas bretylium had no effect on nimmodipinebinding. Only clofillium tended to increase the incidence of spontaneous reversions.

ExcerptReferenceRelevance
"Clofilium was found to inhibit nimodipine binding with an inhibition constant of approximately 5 microM, whereas bretylium had no effect on nimodipine binding."( Molecular basis for the inhibition of 1,4-dihydropyridine calcium channel drugs binding to their receptors by a nonspecific site interaction mechanism.
Herbette, LG; Mason, RP; Skita, V; Young, HS, 1992
)
1
"Only clofilium tended to increase the incidence of spontaneous reversions."( Effects of antiarrhythmic agents on isoproterenol-induced ventricular fibrillation in heavy rats: a possible model of sudden cardiac death.
Balazs, T; Ehrreich, SJ; el-Hage, AN; Johnson, GL, 1986
)
0.73

Treatment

ExcerptReferenceRelevance
"Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery."( Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.
David, I; Dorian, P; Feindel, C; Wang, M, 1991
)
1.28

Bioavailability

ExcerptReferenceRelevance
" The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity."( Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery.
Barnes, SW; Bonamy, GM; Bopp, SE; Borboa, R; Bright, AT; Chatterjee, A; Che, J; Cohen, S; Dharia, NV; Diagana, TT; Fidock, DA; Froissard, P; Gagaring, K; Gettayacamin, M; Glynne, RJ; Gordon, P; Groessl, T; Kato, N; Kuhen, KL; Lee, MC; Mazier, D; McNamara, CW; Meister, S; Nagle, A; Nam, TG; Plouffe, DM; Richmond, W; Roland, J; Rottmann, M; Sattabongkot, J; Schultz, PG; Tuntland, T; Walker, JR; Winzeler, EA; Wu, T; Zhou, B; Zhou, Y, 2011
)
0.37

Dosage Studied

ExcerptRelevanceReference
" Agents were compared over dosage ranges that produced maximal increases in QTc interval and monophasic action potential duration (MAPD)."( Comparative assessment of ibutilide, D-sotalol, clofilium, E-4031, and UK-68,798 in a rabbit model of proarrhythmia.
Brunden, MN; Buchanan, LV; Gibson, JK; Kabell, G, 1993
)
0.54
" The dose-response curve for the inhibition of ISS by isoprenaline was positioned to the left of that for the calcium current."( Characterization of a beta-adrenergically inhibited K+ current in rat cardiac ventricular cells.
Scamps, F, 1996
)
0.29
" Although prazosin (10 microg/kg/min) markedly shifted the phenylephrine (alpha(1)-agonist) dose-response curve to the right, it did not have any effect on clofilium-induced prolongation of QTc and MAPD(90) (43 +/- 7 and 53 +/- 9%, respectively) or the occurrence of TdP (seven of eight)."( Antitorsadogenic effects of ({+/-})-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazine (ranolazine) in anesthetized rabbits.
Belardinelli, L; Dhalla, AK; Robertson, C; Wang, WQ, 2008
)
0.54
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (2)

ClassDescription
organic amino compoundA compound formally derived from ammonia by replacing one, two or three hydrogen atoms by organyl groups.
benzenesAny benzenoid aromatic compound consisting of the benzene skeleton and its substituted derivatives.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)0.08130.00091.901410.0000AID240820; AID576612
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (22)

Processvia Protein(s)Taxonomy
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (12)

Processvia Protein(s)Taxonomy
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (26)

Assay IDTitleYearJournalArticle
AID1346656Mouse K2P5.1 (Two P domain potassium channels)2001The Journal of biological chemistry, Nov-16, Volume: 276, Issue:46
Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume.
AID1346684Human Kv1.5 (Voltage-gated potassium channels)1995Molecular pharmacology, Jan, Volume: 47, Issue:1
Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel.
AID1346732Human Kv10.1 (Voltage-gated potassium channels)2003British journal of pharmacology, Jan, Volume: 138, Issue:1
Inhibition of hEAG1 and hERG1 potassium channels by clofilium and its tertiary analogue LY97241.
AID1346445Human KNa1.1 (Calcium- and sodium-activated potassium channels)2012Biologics : targets & therapy, , Volume: 6Clofilium inhibits Slick and Slack potassium channels.
AID1346458Human KNa1.2 (Calcium- and sodium-activated potassium channels)2012Biologics : targets & therapy, , Volume: 6Clofilium inhibits Slick and Slack potassium channels.
AID58012The compound was evaluated the change in blood pressure at 10 mg/kg active dose1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID220495In vitro activity in isolated canine cardiac Purkinje fibers given as maximum change in APD95 from control value at 10 uM of concentration1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID77824The maximum percent change in the maximum rate rise of the action Potential in Guinea pig right ventricular papillary muscles, at compound concentration 1-10 uM; NS=Not significant1990Journal of medicinal chemistry, Mar, Volume: 33, Issue:3
4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents.
AID75196Concentration (1-10 uM) that causes 10% prolongation in the action potential duration at 90% polarization in Guinea pig right ventricular papillary muscles1990Journal of medicinal chemistry, Mar, Volume: 33, Issue:3
4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents.
AID76510Maximum percent increase in 90% repolarization at a concentration of 10 uM in Guinea pig right ventricular papillary muscles1990Journal of medicinal chemistry, Mar, Volume: 33, Issue:3
4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents.
AID58008The compound was evaluated for the change in blood pressure at MED for 0.1-10 dose range in PES model1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID220496In vitro activity in isolated canine cardiac Purkinje fibers given as 20 percent increase or decrease in action potential duration1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID55776Concentration required for 20% increase in the functional refractory period of canine ventricular muscle (extracellular electrophysiology) in vitro was reported;NR=at 10 uM the FRP was increased 13%1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Rational design of 4-[(methylsulfonyl)amino]benzamides as class III antiarrhythmic agents.
AID60841The compound was evaluated the change in functional refractory period at 10 mg/kg active dose1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID576612Inhibition of human ERG2011European journal of medicinal chemistry, Feb, Volume: 46, Issue:2
Predicting hERG activities of compounds from their 3D structures: development and evaluation of a global descriptors based QSAR model.
AID240820Inhibitory concentration against IKr potassium channel2004Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18
The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents.
AID218876In vitro electrophysiological activity in isolated canine cardiac ventricular muscle tissue given as maximum change in FRP from control value at 100 uM concentration1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID60492Efficacy in blocking sustained ventricular tachycardia (rate>250 bpm) elicited by programmed electrical stimulation in conscious dogs after iv administration of dose 1 mg/kg; no. of successful exp / total no. of exp = 5/61987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Rational design of 4-[(methylsulfonyl)amino]benzamides as class III antiarrhythmic agents.
AID58683The compound was evaluated for the change in heart rate at MED for 0.1-10 dose range in PES model1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID55756Concentration required for 20% increase in action potential duration of canine Purkinje fiber (intracellular electrophysiology) in vitro measured at 95% repolarization was reported. Range is between 0.03-21987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Rational design of 4-[(methylsulfonyl)amino]benzamides as class III antiarrhythmic agents.
AID58807The compound was evaluated the change in heart rate at 10 mg/kg active dose1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID60357Efficacy in blocking sustained ventricular tachycardia (rate>250 bpm) elicited by programmed electrical stimulation in anesthetized dogs after iv administration of dose 0.3 mg/kg; no. of successful exp / total no. of exp = 7/101987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Rational design of 4-[(methylsulfonyl)amino]benzamides as class III antiarrhythmic agents.
AID63278Decrease in Vmax in isolated canine Purkinje fibers at 10 uM1987Journal of medicinal chemistry, May, Volume: 30, Issue:5
Rational design of 4-[(methylsulfonyl)amino]benzamides as class III antiarrhythmic agents.
AID59402The compound was evaluated for the mean effective dose for antiarrhythmic efficacy in PES model1987Journal of medicinal chemistry, Dec, Volume: 30, Issue:12
Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID602156Novartis GNF Liver Stage Dataset: Malariabox Annotation2011Science (New York, N.Y.), Dec-09, Volume: 334, Issue:6061
Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (138)

TimeframeStudies, This Drug (%)All Drugs %
pre-199021 (15.22)18.7374
1990's60 (43.48)18.2507
2000's35 (25.36)29.6817
2010's20 (14.49)24.3611
2020's2 (1.45)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.35

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index25.35 (24.57)
Research Supply Index4.96 (2.92)
Research Growth Index4.69 (4.65)
Search Engine Demand Index24.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.35)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.71%)5.53%
Reviews1 (0.71%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other138 (98.57%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]