Page last updated: 2024-12-11

ditekiren

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

Description

ditekiren: orally active renin inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5464201
CHEMBL ID303323
CHEMBL ID1790497
SCHEMBL ID122368
MeSH IDM0145103

Synonyms (35)

Synonym
l-histidinamide, 1-((1,1-dimethylethoxy)carbonyl)-l-prolyl-l-phenylalanyl-n-(2-hydroxy-5-methyl-1-(2-methylpropyl)-4-(((2-methyl-1-(((2-pyridinylmethyl)amino)carbonyl)butyl)amino)carbonyl)hexyl)-n(sup alpha)-methyl-, (1s-(1r*,2r*,4r*(1r*,2r*)))-
ditekirenum [inn-latin]
ditiquireno [inn-spanish]
tert-butyl (2s)-2-(((alphas)-alpha-(((1s)-1-(((1s,2s,4s)-2-hydroxy-1-isobutyl-5-methyl-4-(((1s,2s)-2-methyl-1-((2-pyridylmethyl)carbamoyl)butyl)carbamoyl)hexyl)carbamoyl)-2-imidazol-4-ylethyl)methylcarbamoyl)phenethyl)carbamoyl)-1-pyrrolidinecarboxylate
ditekiren [usan:inn]
ditekiren
l-histidinamide, 1-((1,1-dimethylethoxy)carbonyl)-l-prolyl-l-phenylalanyl-n-(2-hydroxy-5-methyl-1-(2-methylpropyl)-4-(((2-methyl-1-(((2-pyridinylemthyl)amino)carbonyl)butyl)amino)carbonyl)hexyl)-nalpha-methyl-, (1s-(1r*,2r*,4r*(1r*,2r*)))-
ditekirene [inn-french]
ditekiren (usan)
D03741
103336-05-6
u-71038
u 71038
tert-butyl (2s)-2-[[(2s)-1-[[(2s)-1-[[(4s,5s,7s)-5-hydroxy-2,8-dimethyl-7-[[(2s,3s)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]carbamoyl]nonan-4-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]p
bdbm50024156
chembl303323
2-(1-{[1-(2-hydroxy-1-isobutyl-5-methyl-4-{2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-hexylcarbamoyl)-2-(3h-imidazol-4-yl)-ethyl]-methyl-carbamoyl}-2-phenyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
mcmc-6317
CHEMBL1790497 ,
unii-5355s3w1is
ditekirenum
ditekirene
5355s3w1is ,
ditiquireno
bdbm50368278
l-histidinamide, 1-((1,1-dimethylethoxy)carbonyl)-l-prolyl-l-phenylalanyl-n-(2-hydroxy-5-methyl-1-(2-methylpropyl)-4-(((2-methyl-1-(((2-pyridinylmethyl)amino)carbonyl)butyl)amino)carbonyl)hexyl)-n(sup .alpha.)-methyl-, (1s-(1r*,2r*,4r*(1r*,2r*)))-
ditekiren [usan]
ditekiren [inn]
tert-butyl (2s)-2-[[(alphas)-alpha-[[(1s)-1-[[(1s,2s,4s)-2-hydroxy-1-isobutyl-5-methyl-4-[[(1s,2s)-2-methyl-1-[(2-pyridylmethyl)carbamoyl]butyl]carbamoyl]hexyl]carbamoyl]-2-imidazol-4-ylethyl]methylcarbamoyl]phenethyl]carbamoyl]-1-pyrrolidinecarboxylate
SCHEMBL122368
DTXSID40145787
Q27261065
tert-butyl (s)-2-(((4s,7s,9s,10s,13s,16s)-13-((1h-imidazol-4-yl)methyl)-4-((s)-sec-butyl)-9-hydroxy-10-isobutyl-7-isopropyl-14-methyl-3,6,12,15-tetraoxo-17-phenyl-1-(pyridin-2-yl)-2,5,11,14-tetraazaheptadecan-16-yl)carbamoyl)pyrrolidine-1-carboxylate
AT38268
AKOS040746778

Research Excerpts

Overview

Ditekiren is a pseudo-octapeptide being developed as an inhibitor of human renin.

ExcerptReferenceRelevance
"Ditekiren is a pseudo-octapeptide being developed as an inhibitor of human renin. "( Precipitation of the renin inhibitor ditekiren upon i.v. infusion; in vitro studies and their relationship to in vivo precipitation in the cynomolgus monkey.
Cole, SL; Davio, SR; Kakuk, TJ; McShane, MM; Zaya, RM, 1991
)
2

Bioavailability

ExcerptReferenceRelevance
" 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

Dosage Studied

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
)
0.28
" Serum levels for U-71,038 determined 30 min after dosing averaged less than 300 ng equivalents/ml suggesting that less than 1% of the administered dose was in the systemic circulation at that time."( Development of a sensitive activity assay for high-volume evaluation of human renin inhibitory peptides in rat serum: results with U-71,038.
Cook, KJ; Cornette, JC; Evans, DB; Friis, JM; Harris, DW; Lakings, DB; Rush, BD; Ruwart, MJ; Sharma, SK; Wilkinson, KF, 1990
)
0.28
[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)
Pepsin ASus scrofa (pig)IC50 (µMol)6.80000.00702.15078.2000AID156723
ReninHomo sapiens (human)IC50 (µMol)0.00030.00000.77968.2000AID198478
ReninHomo sapiens (human)Ki0.00000.00001.80787.4000AID198986
Cathepsin D Bos taurus (cattle)IC50 (µMol)6.30000.00700.91656.3000AID47824
[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)
Multidrug resistance protein 1aRattus norvegicus (Norway rat)Km19.10005.00005.00005.0000AID681452
[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 (10)

Assay IDTitleYearJournalArticle
AID681668TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: 1 uM, Ditekiren: 20 uM) in Bsep-expressing LLC-PK1 cells2000Molecular pharmacology, Jan, Volume: 57, Issue:1
Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.
AID156723Inhibition of porcine pepsin1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
AID198470Inhibition of human plasma renin1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
AID198512In vitro inhibitory activity against human plasma renin1988Journal of medicinal chemistry, Jan, Volume: 31, Issue:1
Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu psi[CH(OH)CH2]Val or leu psi[CH2NH]Val substitutions.
AID47824Inhibition of bovine cathepsin D1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
AID679778TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: 1 uM, Ditekiren: 20 uM) in MDR1-expressing LLC-PK1 cells2000Molecular pharmacology, Jan, Volume: 57, Issue:1
Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.
AID198478In vitro inhibition of human renin by radio-immuno assay of angiotensin I (ANG I)1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038).
AID17660The dissociation constant determined by fluorescence displacement assay1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038).
AID681452TP_TRANSPORTER: uptake, inhibited by Cyclosporine, Nicardipine, Daunomycin, Verapamil, Reserpine, Rhodamine 123 and Vinblastine in bile canalicular membrane vesicles1997The Journal of pharmacology and experimental therapeutics, Apr, Volume: 281, Issue:1
Characterization of the hepatic canalicular membrane transport of a model oligopeptide: ditekiren.
AID198986In vitro inhibition constants using recombinant human renin assay1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038).
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (23)

TimeframeStudies, This Drug (%)All Drugs %
pre-19906 (26.09)18.7374
1990's16 (69.57)18.2507
2000's1 (4.35)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (3.85%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other25 (96.15%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]