Page last updated: 2024-12-10

almokalant

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

Description

almokalant: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID3033962
CHEMBL ID362103
SCHEMBL ID247121
MeSH IDM0200734

Synonyms (16)

Synonym
4-(3-{ethyl-[3-(propane-1-sulfinyl)-propyl]-amino}-2-hydroxy-propoxy)-benzonitrile
bdbm50151869
almokalant
CHEMBL362103 ,
4-[3-[ethyl(3-propylsulfinylpropyl)amino]-2-hydroxypropoxy]benzonitrile
123955-10-2
SCHEMBL247121
4-[3-[ethyl[3-(propylsulfinyl)-propyl]amino]-2-hydroxypropoxy]benzonitrile
4-[3-[ethyl[3-(propylsulfinyl)propyl]amino]-2-hydroxypropoxy]-benzonitrile
ZMHOBBKJBYLXFR-UHFFFAOYSA-N
HY-106855
CS-0026741
DTXSID40869693
h 234/09
Q1426422
AKOS040741090

Research Excerpts

Overview

Almokalant is a newly developed selective blocker of the delayed outward K+ current. It exhibits the electrophysiological properties of a class III antiarrhythmic agent.

ExcerptReferenceRelevance
"Almokalant is a newly developed selective blocker of the delayed outward K+ current and exhibits the electrophysiological properties of a class III antiarrhythmic agent. "( Effect of almokalant, a selective potassium channel blocker, on the termination and inducibility of paroxysmal supraventricular tachycardias: a study in patients with Wolff-Parkinson-White syndrome and atrioventricular nodal reentrant tachycardia. Almokal
Darpö, B; Edvardsson, N, 1995
)
2.14

Treatment

ExcerptReferenceRelevance
"Almokalant pretreatment increased the number of animals developing no arrythmias (5/9 vs."( Effect of almokalant a specific inhibitor of IKr on myocardial ischaemia-reperfusion induced arrhythmias in rabbits.
Farkas, A; Leprán, I; Papp, JG, 1996
)
1.42

Toxicity

ExcerptReferenceRelevance
" In conclusion, ALM caused embryotoxicity in the mouse, most likely secondary to adverse effects on the embryonic heart."( Developmental toxicity of the class III antiarrhythmic agent almokalant in mice. Adverse effects mediated via induction of embryonic heart rhythm abnormalities.
Danielsson, BR; Sköld, AC, 2000
)
0.55

Pharmacokinetics

Almokalant plasma concentration showed a biphasic decrease with an elimination half-life of 2. The drug has been withdrawn from further clinical development.

ExcerptReferenceRelevance
" Although almokalant has been withdrawn from further clinical development, its metabolic and pharmacokinetic properties have been well characterized."( An assessment of human liver-derived in vitro systems to predict the in vivo metabolism and clearance of almokalant.
Andersson, TB; Boobis, AR; Castell, JV; Corcos, L; Edwards, RJ; Goldfarb, PS; Gómez-Lechón, MJ; Guillouzo, A; Hidestrand, M; Hoffmann, KJ; Ingelman-Sundberg, M; Lake, BG; Lewis, DF; Pelkonen, O; Price, RJ; Renwick, AB; Sjöberg, H; Taavitsainen, P; Watts, P, 2001
)
0.93

Dosage Studied

ExcerptRelevanceReference
" Furthermore, we defined the electrophysiological effects of this dose on the heart, as well as the pharmacokinetics, safety, and tolerance throughout a wide dosing range."( Tolerance and effects of almokalant, a new selective Ik blocking agent, on ventricular repolarization and on sino-atrial and atrioventricular nodal function in the heart: a study in healthy, male volunteers utilizing transesophageal atrial stimulation.
Almgren, O; Bäärnhielm, C; Bergstrand, R; Darpö, B; Edvardsson, N; Gottfridsson, C; Sandstedt, B, 1995
)
0.59
" Dosing on gestational day (GD) 11 was associated with right-sided oblique cleft lip and short tail, while dosing on day 13 caused digital hypoplasia and/or amputation."( Teratogenic potential of almokalant, dofetilide, and d-sotalol: drugs with potassium channel blocking activity.
Brown-Woodman, PD; Danielsson, BR; Snow, MD; Webster, WS, 1996
)
0.6
"Cardiac ventricular septum defects and vascular malformations were observed after dosing on GD 10-11 and, to a lesser degree, on GD 12-13."( Stage-specific skeletal and visceral defects of the I(Kr)-blocker almokalant: further evidence for teratogenicity via a hypoxia-related mechanism.
Danielsson, BR; Sköld, AC; Wellfelt, K, 2001
)
0.55
" Rats were orally dosed with almokalant or tap water on GD 11 (150 micromol/kg), 13 (50 micromol/kg), or 16 (800 micromol/kg), followed by PIM intravenously 30 min later."( Teratogenicity by the hERG potassium channel blocking drug almokalant: use of hypoxia marker gives evidence for a hypoxia-related mechanism mediated via embryonic arrhythmia.
Blomgren, B; Danielsson, BR; Dillner, B; Johansson, A; Sköld, AC, 2003
)
0.85
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Bile salt export pumpHomo sapiens (human)IC50 (µMol)55.75000.11007.190310.0000AID1449628
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)0.12750.00091.901410.0000AID240820; AID386536
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
UDP-glucuronosyltransferase 1A9Homo sapiens (human)Km1,060.00005.00006.830010.0000AID624637
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (53)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processUDP-glucuronosyltransferase 1A9Homo sapiens (human)
retinoic acid metabolic processUDP-glucuronosyltransferase 1A9Homo sapiens (human)
flavone metabolic processUDP-glucuronosyltransferase 1A9Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1A9Homo sapiens (human)
flavonoid glucuronidationUDP-glucuronosyltransferase 1A9Homo sapiens (human)
xenobiotic glucuronidationUDP-glucuronosyltransferase 1A9Homo sapiens (human)
liver developmentUDP-glucuronosyltransferase 1A9Homo sapiens (human)
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
lipid metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
androgen metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 2B7Homo sapiens (human)
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 (23)

Processvia Protein(s)Taxonomy
retinoic acid bindingUDP-glucuronosyltransferase 1A9Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1A9Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1A9Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1A9Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1A9Homo sapiens (human)
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 2B7Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 2B7Homo sapiens (human)
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 (17)

Processvia Protein(s)Taxonomy
endoplasmic reticulumUDP-glucuronosyltransferase 1A9Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1A9Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A9Homo sapiens (human)
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
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 (6)

Assay IDTitleYearJournalArticle
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.
AID386536Inhibition of human ERG potassium channel2008Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7
A binary QSAR model for classification of hERG potassium channel blockers.
AID384955Intrinsic aqueous solubility at pH 10 by shake-flask method2008Journal of medicinal chemistry, May-22, Volume: 51, Issue:10
Molecular characteristics for solid-state limited solubility.
AID624640Drug glucuronidation reaction catalyzed by human recombinant UGT2B72005Pharmacology & therapeutics, Apr, Volume: 106, Issue:1
UDP-glucuronosyltransferases and clinical drug-drug interactions.
AID1449628Inhibition of human BSEP expressed in baculovirus transfected fall armyworm Sf21 cell membranes vesicles assessed as reduction in ATP-dependent [3H]-taurocholate transport into vesicles incubated for 5 mins by Topcount based rapid filtration method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
AID624637Drug glucuronidation reaction catalyzed by human recombinant UGT1A92005Pharmacology & therapeutics, Apr, Volume: 106, Issue:1
UDP-glucuronosyltransferases and clinical drug-drug interactions.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (68)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's43 (63.24)18.2507
2000's21 (30.88)29.6817
2010's4 (5.88)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 17.42

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 Index17.42 (24.57)
Research Supply Index4.34 (2.92)
Research Growth Index4.13 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (17.42)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (8.57%)5.53%
Reviews2 (2.86%)6.00%
Case Studies2 (2.86%)4.05%
Observational0 (0.00%)0.25%
Other60 (85.71%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]