Page last updated: 2024-12-06

enalkiren

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

Enalkiren is a selective, non-peptide, orally active renin inhibitor. It acts by binding to the active site of renin, preventing the conversion of angiotensinogen to angiotensin I. This inhibition reduces the production of angiotensin II, a potent vasoconstrictor and aldosterone stimulator. Enalkiren has been studied for its potential to treat hypertension and other cardiovascular diseases. It has shown promising results in clinical trials, demonstrating a significant reduction in blood pressure and improvement in cardiovascular outcomes. However, enalkiren's development has been discontinued due to concerns about its safety profile. Further research is needed to explore its potential therapeutic applications.'

Cross-References

ID SourceID
PubMed CID60594
CHEMBL ID300337
CHEBI ID4787
SCHEMBL ID123107
MeSH IDM0158781

Synonyms (39)

Synonym
abbott-64662
a-64662
enalkiren (usan/inn)
D03738
enalkiren
C07466
a 64662
113082-98-7
DB03395
l-histidinamide, n-(3-amino-3-methyl-1-oxobutyl)-o-methyl-l-tyrosyl-n-(1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl)-, (1s-(1r*,2s*,3r*))-
enalquireno [inn-spanish]
(alphas)-alpha-((alphas)-alpha-(3-amino-3-methylbutyramido)-p-methoxyhydrocinnamamido)-n-((1s,2r,3s)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl)imidazole-4-propionamide
enalkiren [usan:inn]
enalkirene [inn-french]
enalkirenum [inn-latin]
abbott 64662
chebi:4787 ,
CHEMBL300337 ,
3-amino-n-[(2s)-1-[[(2s)-1-[[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]-3-methylbutanamide
bdbm50006202
3-amino-n-[1-[1-(1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-(1h-imidazol-4-yl)-ethylcarbamoyl]-2-(4-methoxy-phenyl)-ethyl]-3-methyl-butyramide
enalquireno
0u7yz42z47 ,
unii-0u7yz42z47
enalkirenum
enalkirene
enalkiren [mart.]
enalkiren [inn]
(.alpha.s)-.alpha.-((.alpha.s)-.alpha.-(3-amino-3-methylbutyramido)-p-methoxyhydrocinnamamido)-n-((1s,2r,3s)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl)imidazole-4-propionamide
l-histidinamide, n-(3-amino-3-methyl-1-oxobutyl)-o-methyl-l-tyrosyl-n-((1s,2r,3s)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl)-
enalkiren [usan]
SCHEMBL123107
3-amino-n-[(1s)-2-[[(1s)-2-[[(1s,2r,3s)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methyl-hexyl]amino]-1-(1h-imidazol-5-ylmethyl)-2-oxo-ethyl]amino]-1-[(4-methoxyphenyl)methyl]-2-oxo-ethyl]-3-methyl-butanamide
DTXSID10150282
Q27094330
HY-105276
CS-0024915
3-amino-n-((s)-1-(((s)-1-(((2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl)amino)-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-3-methylbutanamide
AKOS040748319

Research Excerpts

Effects

ExcerptReferenceRelevance
"Enalkiren has been shown to produce dose-related suppression of plasma renin activity (PRA) and angiotensin II when administered intravenously."( Clinical pharmacology of enalkiren, a novel, dipeptide renin inhibitor.
Boger, RS; Glassman, HN; Griffiths, AN; Kleinert, HD; Luther, RR; Moyse, DM, 1990
)
1.3

Pharmacokinetics

ExcerptReferenceRelevance
" To relate the temporal relationship of effect changes accurately to plasma drug levels, a pharmacokinetic model was combined with a pharmacokinetic model that incorporated a hypothetical effect compartment."( Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a new renin inhibitor). I: Single dose study.
Boger, RS; Granneman, GR; Gupta, SK; Hollenberg, NK; Luther, RR,
)
0.36

Bioavailability

ExcerptReferenceRelevance
" In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey."( C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.
Armiger, YL; Baker, WR; Barlow, JL; Boyd, SA; Cohen, J; Egan, DA; Fung, AK; Klinghofer, V; Mantei, RA; Stein, HH, 1992
)
0.28
" New generation renin inhibitors with higher potency and greater oral bioavailability may join the antihypertensive armamentarium."( Renin inhibitors in hypertension.
Boger, RS; Glassman, HN; Luther, RR, 1991
)
0.28
"A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors."( Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
Barlow, JL; Cohen, J; Egan, DA; Martin, DL; Polakowski, J; Rosenberg, SH; Spina, KP; Stein, HH; Woods, KW; Yao, Z, 1993
)
0.29

Dosage Studied

Enalkiren (A-64662) in patients with congestive heart failure. A prolonged hypotensive effect is seen following single doses of enalkiren and RO 42-5892. Repeated dosing with enalkirens results in sustained hypotensive effects without tachyphylaxis.

ExcerptRelevanceReference
" A prolonged hypotensive effect is seen following single doses of enalkiren and RO 42-5892, and repeated dosing with enalkiren results in sustained hypotensive effect without tachyphylaxis."( Renin inhibitors in hypertension.
Boger, RS; Glassman, HN; Luther, RR, 1991
)
0.52
" infusion dosing of enalkiren (A-64662) in patients with congestive heart failure."( Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a renin inhibitor). II: A dose-ranging study in patients with congestive heart failure.
Boger, RS; Granneman, GR; Gupta, SK; Packer, M, 1993
)
0.84
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
peptideAmide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another with formal loss of water. The term is usually applied to structures formed from alpha-amino acids, but it includes those derived from any amino carboxylic acid. X = OH, OR, NH2, NHR, etc.
[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 (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Pepsin ASus scrofa (pig)IC50 (µMol)100.00000.00702.15078.2000AID156903
ReninHomo sapiens (human)IC50 (µMol)0.00080.00000.77968.2000AID195442
Cathepsin D Bos taurus (cattle)IC50 (µMol)50.50000.00700.91656.3000AID47825; AID47842
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (18)

Processvia Protein(s)Taxonomy
kidney developmentReninHomo sapiens (human)
mesonephros developmentReninHomo sapiens (human)
angiotensin maturationReninHomo sapiens (human)
renin-angiotensin regulation of aldosterone productionReninHomo sapiens (human)
proteolysisReninHomo sapiens (human)
regulation of blood pressureReninHomo sapiens (human)
male gonad developmentReninHomo sapiens (human)
hormone-mediated signaling pathwayReninHomo sapiens (human)
response to lipopolysaccharideReninHomo sapiens (human)
response to immobilization stressReninHomo sapiens (human)
drinking behaviorReninHomo sapiens (human)
regulation of MAPK cascadeReninHomo sapiens (human)
cell maturationReninHomo sapiens (human)
amyloid-beta metabolic processReninHomo sapiens (human)
response to cAMPReninHomo sapiens (human)
response to cGMPReninHomo sapiens (human)
cellular response to xenobiotic stimulusReninHomo sapiens (human)
juxtaglomerular apparatus developmentReninHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
aspartic-type endopeptidase activityReninHomo sapiens (human)
signaling receptor bindingReninHomo sapiens (human)
insulin-like growth factor receptor bindingReninHomo sapiens (human)
protein bindingReninHomo sapiens (human)
peptidase activityReninHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (6)

Processvia Protein(s)Taxonomy
extracellular regionReninHomo sapiens (human)
extracellular spaceReninHomo sapiens (human)
plasma membraneReninHomo sapiens (human)
apical part of cellReninHomo sapiens (human)
extracellular spaceReninHomo sapiens (human)
extracellular regionCathepsin D Bos taurus (cattle)
lysosomeCathepsin D Bos taurus (cattle)
melanosomeCathepsin D Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (14)

Assay IDTitleYearJournalArticle
AID125833Maximum fall in mean arterial blood pressure expressed in mmHg following a 30 mg/kg dose in monkeys.1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
Renin inhibitors containing esters at the P2-position. Oral activity in a derivative of methyl aminomalonate.
AID195613Inhibition of monkey plasma renin1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
Renin inhibitors containing esters at the P2-position. Oral activity in a derivative of methyl aminomalonate.
AID10250Bioavailability in monkey (i.d. dosing)1992Journal of medicinal chemistry, May-15, Volume: 35, Issue:10
C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.
AID21683Plasma level by the renin inhibition assay from samples taken at 30 minutes from portal circulation by administering 10 mg/kg intraduodenally to the rat1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
AID198669Inhibitory activity against human plasma renin at pH 7.41990Journal of medicinal chemistry, Jul, Volume: 33, Issue:7
Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action.
AID47825Compound was evaluated for the percent inhibition of Cathepsin D in Bovine1992Journal of medicinal chemistry, Jul-10, Volume: 35, Issue:14
Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors.
AID21681Plasma level by the renin inhibition assay from samples taken at 10 minutes from portal circulation by administering 10 mg/kg intraduodenally to the rat1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
AID21684Plasma level by the renin inhibition assay from samples taken at 30 minutes from systemic circulation by administering 10 mg/kg intraduodenally to the rat1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
AID198472Inhibition of human plasma renin at pH 7.41993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
AID195442In vitro inhibition of monkey renin.1992Journal of medicinal chemistry, Jul-10, Volume: 35, Issue:14
Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors.
AID156903Compound was evaluated for the percent inhibition of pepsin1992Journal of medicinal chemistry, Jul-10, Volume: 35, Issue:14
Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors.
AID21682Plasma level by the renin inhibition assay from samples taken at 10 minutes from systemic circulation by administering 10 mg/kg intraduodenally to the rat1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
AID195453Inhibitory activity against renin in monkey plasma at pH 7.71992Journal of medicinal chemistry, May-15, Volume: 35, Issue:10
C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.
AID47842Inhibition of Bovine Cathepsin D.1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
Renin inhibitors containing esters at the P2-position. Oral activity in a derivative of methyl aminomalonate.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (39)

TimeframeStudies, This Drug (%)All Drugs %
pre-19905 (12.82)18.7374
1990's31 (79.49)18.2507
2000's2 (5.13)29.6817
2010's1 (2.56)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: 29.50

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 Index29.50 (24.57)
Research Supply Index3.83 (2.92)
Research Growth Index4.98 (4.65)
Search Engine Demand Index36.71 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (29.50)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (12.50%)5.53%
Reviews7 (17.50%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other28 (70.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]