Page last updated: 2024-11-08

mln 4760

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Description

2-(1-carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)ethylamino)-4-methylpentanoic acid: MLN-4760 is the (S,S)-isomer; an ACE2 inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

MLN-4760 : A L-histidine derivative that is L-histidine in which a hydrogen of the primary amino group is substituted by a (1S)-1-carboxy-3-methylbutyl group and the ring NH group is substituted by a 3,5-dichlorobenzyl group. It is a potent and selective human angiotensin-converting enzyme 2 (ACE2) inhibitor (IC50 = 0.44 nM) which was in clinical development for the treatment of ulcerative colitis. [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]

Cross-References

ID SourceID
PubMed CID448281
CHEMBL ID429844
CHEBI ID166834
SCHEMBL ID1691048
MeSH IDM0466824

Synonyms (39)

Synonym
ore-1001 free acid
305335-31-3
ore1001
n-[(1s)-1-carboxy-3-methylbutyl]-3-(3,5-dichlorobenzyl)-l-histidine
CHEBI:166834
gl1001 ,
ore-1001
2(s)-(1(s)-carboxy-2-(3-(3,5-dichlorobenzyl)-3h-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid
xx5 ,
(s,s)-2-{1-carboxy-2-[3-(3,5-dichloro-benzyl)-3h-imidazol-4-yl]-ethylamino}-4-methyl-pentanoic acid
2-(1-carboxy-2-(3-(3,5-dichlorobenzyl)-3h-imidazol-4-yl)ethylamino)-4-methylpentanoic acid
(2s)-2-{[(1s)-1-carboxy-2-{1-[(3,5-dichlorophenyl)methyl]-1h-imidazol-5-yl}ethyl]amino}-4-methylpentanoic acid
mln4760
mln 4760
bdbm21489
chembl429844 ,
mln-4760
GL-1001 ,
(2s)-2-[[(2s)-3-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]-1-hydroxy-1-oxopropan-2-yl]amino]-4-methylpentanoic acid
unii-4ld0zhv25k
4ld0zhv25k ,
S8940
gtpl7866
l-histidine, n-((1s)-1-carboxy-3-methylbutyl)-3-((3,5-dichlorophenyl)methyl)-
SCHEMBL1691048
CS-0015513
HY-19414
DTXSID70184609
DB12271
EC-000.2483
Q27087273
A16884
(2s)-2-[[(1s)-1-carboxy-2-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]ethyl]amino]-4-methylpentanoic acid
MS-27570
EX-A3296
((s)-1-carboxy-2-(1-(3,5-dichlorobenzyl)-1h-imidazol-5-yl)ethyl)-l-leucine
(S)-2-(((S)-1-CARBOXY-2-(1-(3,5-DICHLOROBENZYL)-1H-IMIDAZOL-5-YL)ETHYL)AMINO)-4-METHYLPENTANOIC ACID
EN300-22203532
AKOS040742161
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
anti-inflammatory agentAny compound that has anti-inflammatory effects.
EC 3.4.17.23 (angiotensin-converting enzyme 2) inhibitorAny EC 3.4.17.* (metallocarboxypeptidase) inhibitor that inhibits the action of angiotensin-converting enzyme 2 (EC 3.4.17.23).
[role 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]

Drug Classes (3)

ClassDescription
L-histidine derivativeA proteinogenic amino acid derivative resulting from the formal reaction of L-histidine at the amino group, carboxy group, or the imidazolyl moiety, or from the replacement of any hydrogen of L-histidine by a heteroatom.
dichlorobenzeneAny member of the class of chlorobenzenes carrying two chloro groups at unspecified positions.
L-leucine derivativeA proteinogenic amino acid derivative resulting from reaction of L-leucine at the amino group or the carboxy group, or from the replacement of any hydrogen of L-leucine by a heteroatom.
[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 (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Carboxypeptidase A1Bos taurus (cattle)IC50 (µMol)27.00002.73002.74502.7600AID1798090
Angiotensin-converting enzyme Homo sapiens (human)IC50 (µMol)10.00000.00010.533610.0000AID1916553
Type-1A angiotensin II receptor Rattus norvegicus (Norway rat)IC50 (µMol)0.00040.00040.15553.8000AID1560682
Angiotensin-converting enzyme 2 Homo sapiens (human)IC50 (µMol)16.66860.00042.207910.0000AID1560682; AID1798089; AID1916554; AID314432; AID331168
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (79)

Processvia Protein(s)Taxonomy
leukotriene metabolic processCarboxypeptidase A1Bos taurus (cattle)
response to hypoxiaAngiotensin-converting enzyme Homo sapiens (human)
kidney developmentAngiotensin-converting enzyme Homo sapiens (human)
blood vessel remodelingAngiotensin-converting enzyme Homo sapiens (human)
angiotensin maturationAngiotensin-converting enzyme Homo sapiens (human)
regulation of renal output by angiotensinAngiotensin-converting enzyme Homo sapiens (human)
neutrophil mediated immunityAngiotensin-converting enzyme Homo sapiens (human)
antigen processing and presentation of peptide antigen via MHC class IAngiotensin-converting enzyme Homo sapiens (human)
regulation of systemic arterial blood pressure by renin-angiotensinAngiotensin-converting enzyme Homo sapiens (human)
proteolysisAngiotensin-converting enzyme Homo sapiens (human)
spermatogenesisAngiotensin-converting enzyme Homo sapiens (human)
female pregnancyAngiotensin-converting enzyme Homo sapiens (human)
regulation of blood pressureAngiotensin-converting enzyme Homo sapiens (human)
male gonad developmentAngiotensin-converting enzyme Homo sapiens (human)
response to xenobiotic stimulusAngiotensin-converting enzyme Homo sapiens (human)
embryo development ending in birth or egg hatchingAngiotensin-converting enzyme Homo sapiens (human)
post-transcriptional regulation of gene expressionAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of gene expressionAngiotensin-converting enzyme Homo sapiens (human)
substance P catabolic processAngiotensin-converting enzyme Homo sapiens (human)
bradykinin catabolic processAngiotensin-converting enzyme Homo sapiens (human)
regulation of smooth muscle cell migrationAngiotensin-converting enzyme Homo sapiens (human)
regulation of vasoconstrictionAngiotensin-converting enzyme Homo sapiens (human)
animal organ regenerationAngiotensin-converting enzyme Homo sapiens (human)
response to nutrient levelsAngiotensin-converting enzyme Homo sapiens (human)
response to lipopolysaccharideAngiotensin-converting enzyme Homo sapiens (human)
mononuclear cell proliferationAngiotensin-converting enzyme Homo sapiens (human)
response to laminar fluid shear stressAngiotensin-converting enzyme Homo sapiens (human)
angiotensin-activated signaling pathwayAngiotensin-converting enzyme Homo sapiens (human)
vasoconstrictionAngiotensin-converting enzyme Homo sapiens (human)
hormone metabolic processAngiotensin-converting enzyme Homo sapiens (human)
hormone catabolic processAngiotensin-converting enzyme Homo sapiens (human)
eating behaviorAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of apoptotic processAngiotensin-converting enzyme Homo sapiens (human)
peptide catabolic processAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of vasoconstrictionAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of glucose importAngiotensin-converting enzyme Homo sapiens (human)
regulation of synaptic plasticityAngiotensin-converting enzyme Homo sapiens (human)
lung alveolus developmentAngiotensin-converting enzyme Homo sapiens (human)
amyloid-beta metabolic processAngiotensin-converting enzyme Homo sapiens (human)
arachidonic acid secretionAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of neurogenesisAngiotensin-converting enzyme Homo sapiens (human)
heart contractionAngiotensin-converting enzyme Homo sapiens (human)
regulation of angiotensin metabolic processAngiotensin-converting enzyme Homo sapiens (human)
hematopoietic stem cell differentiationAngiotensin-converting enzyme Homo sapiens (human)
angiogenesis involved in coronary vascular morphogenesisAngiotensin-converting enzyme Homo sapiens (human)
cellular response to glucose stimulusAngiotensin-converting enzyme Homo sapiens (human)
response to dexamethasoneAngiotensin-converting enzyme Homo sapiens (human)
cell proliferation in bone marrowAngiotensin-converting enzyme Homo sapiens (human)
regulation of heart rate by cardiac conductionAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of calcium ion importAngiotensin-converting enzyme Homo sapiens (human)
response to thyroid hormoneAngiotensin-converting enzyme Homo sapiens (human)
blood vessel diameter maintenanceAngiotensin-converting enzyme Homo sapiens (human)
regulation of hematopoietic stem cell proliferationAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of gap junction assemblyAngiotensin-converting enzyme Homo sapiens (human)
cellular response to aldosteroneAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of peptidyl-cysteine S-nitrosylationAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of systemic arterial blood pressureAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of signaling receptor activityAngiotensin-converting enzyme 2 Homo sapiens (human)
symbiont entry into host cellAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of cytokine productionAngiotensin-converting enzyme 2 Homo sapiens (human)
angiotensin maturationAngiotensin-converting enzyme 2 Homo sapiens (human)
angiotensin-mediated drinking behaviorAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of systemic arterial blood pressure by renin-angiotensinAngiotensin-converting enzyme 2 Homo sapiens (human)
tryptophan transportAngiotensin-converting enzyme 2 Homo sapiens (human)
viral life cycleAngiotensin-converting enzyme 2 Homo sapiens (human)
receptor-mediated endocytosis of virus by host cellAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of vasoconstrictionAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of transmembrane transporter activityAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of cell population proliferationAngiotensin-converting enzyme 2 Homo sapiens (human)
symbiont entry into host cellAngiotensin-converting enzyme 2 Homo sapiens (human)
receptor-mediated virion attachment to host cellAngiotensin-converting enzyme 2 Homo sapiens (human)
negative regulation of smooth muscle cell proliferationAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of inflammatory responseAngiotensin-converting enzyme 2 Homo sapiens (human)
positive regulation of amino acid transportAngiotensin-converting enzyme 2 Homo sapiens (human)
maternal process involved in female pregnancyAngiotensin-converting enzyme 2 Homo sapiens (human)
positive regulation of cardiac muscle contractionAngiotensin-converting enzyme 2 Homo sapiens (human)
membrane fusionAngiotensin-converting enzyme 2 Homo sapiens (human)
negative regulation of ERK1 and ERK2 cascadeAngiotensin-converting enzyme 2 Homo sapiens (human)
blood vessel diameter maintenanceAngiotensin-converting enzyme 2 Homo sapiens (human)
entry receptor-mediated virion attachment to host cellAngiotensin-converting enzyme 2 Homo sapiens (human)
positive regulation of gap junction assemblyAngiotensin-converting enzyme 2 Homo sapiens (human)
regulation of cardiac conductionAngiotensin-converting enzyme 2 Homo sapiens (human)
positive regulation of L-proline import across plasma membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
positive regulation of reactive oxygen species metabolic processAngiotensin-converting enzyme 2 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (20)

Processvia Protein(s)Taxonomy
metallocarboxypeptidase activityCarboxypeptidase A1Bos taurus (cattle)
zinc ion bindingCarboxypeptidase A1Bos taurus (cattle)
endopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
carboxypeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
metalloendopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
calmodulin bindingAngiotensin-converting enzyme Homo sapiens (human)
peptidase activityAngiotensin-converting enzyme Homo sapiens (human)
metallopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
exopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
tripeptidyl-peptidase activityAngiotensin-converting enzyme Homo sapiens (human)
peptidyl-dipeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
zinc ion bindingAngiotensin-converting enzyme Homo sapiens (human)
chloride ion bindingAngiotensin-converting enzyme Homo sapiens (human)
mitogen-activated protein kinase kinase bindingAngiotensin-converting enzyme Homo sapiens (human)
bradykinin receptor bindingAngiotensin-converting enzyme Homo sapiens (human)
mitogen-activated protein kinase bindingAngiotensin-converting enzyme Homo sapiens (human)
metallodipeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
heterocyclic compound bindingAngiotensin-converting enzyme Homo sapiens (human)
virus receptor activityAngiotensin-converting enzyme 2 Homo sapiens (human)
endopeptidase activityAngiotensin-converting enzyme 2 Homo sapiens (human)
carboxypeptidase activityAngiotensin-converting enzyme 2 Homo sapiens (human)
metallocarboxypeptidase activityAngiotensin-converting enzyme 2 Homo sapiens (human)
protein bindingAngiotensin-converting enzyme 2 Homo sapiens (human)
metallopeptidase activityAngiotensin-converting enzyme 2 Homo sapiens (human)
peptidyl-dipeptidase activityAngiotensin-converting enzyme 2 Homo sapiens (human)
zinc ion bindingAngiotensin-converting enzyme 2 Homo sapiens (human)
identical protein bindingAngiotensin-converting enzyme 2 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (17)

Processvia Protein(s)Taxonomy
extracellular spaceAngiotensin-converting enzyme Homo sapiens (human)
extracellular regionAngiotensin-converting enzyme Homo sapiens (human)
extracellular spaceAngiotensin-converting enzyme Homo sapiens (human)
lysosomeAngiotensin-converting enzyme Homo sapiens (human)
endosomeAngiotensin-converting enzyme Homo sapiens (human)
plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
external side of plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
basal plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
brush border membraneAngiotensin-converting enzyme Homo sapiens (human)
extracellular exosomeAngiotensin-converting enzyme Homo sapiens (human)
sperm midpieceAngiotensin-converting enzyme Homo sapiens (human)
plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
plasma membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
extracellular regionAngiotensin-converting enzyme 2 Homo sapiens (human)
extracellular spaceAngiotensin-converting enzyme 2 Homo sapiens (human)
endoplasmic reticulum lumenAngiotensin-converting enzyme 2 Homo sapiens (human)
plasma membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
ciliumAngiotensin-converting enzyme 2 Homo sapiens (human)
cell surfaceAngiotensin-converting enzyme 2 Homo sapiens (human)
membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
apical plasma membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
endocytic vesicle membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
brush border membraneAngiotensin-converting enzyme 2 Homo sapiens (human)
membrane raftAngiotensin-converting enzyme 2 Homo sapiens (human)
extracellular exosomeAngiotensin-converting enzyme 2 Homo sapiens (human)
extracellular spaceAngiotensin-converting enzyme 2 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (12)

Assay IDTitleYearJournalArticle
AID1916553Inhibition of recombinant human ACE using Mca-RPGFSAFK (Dnp)- OH as substrate by fluorescence plate reader assay2021Bioorganic & medicinal chemistry, 10-15, Volume: 48Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection.
AID1916556Inhibition of ACE2 in human MNCs assessed as maximum inhibition using 7- Mca-YVADAPK (Dnp) as substrate by fluorescence plate reader assay relative to control2021Bioorganic & medicinal chemistry, 10-15, Volume: 48Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection.
AID314432Inhibition of ACE22008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
Thiol-based angiotensin-converting enzyme 2 inhibitors: P1' modifications for the exploration of the S1' subsite.
AID331168Inhibition of ACE22008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Development of potent and selective phosphinic peptide inhibitors of angiotensin-converting enzyme 2.
AID1560682Inhibition of ACE2 (unknown origin)2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
The Other Angiotensin II Receptor: AT
AID1916554Inhibition of recombinant human ACE2 using 7-Mca-YVADAPK (Dnp) as substrate by fluorescence plate reader assay2021Bioorganic & medicinal chemistry, 10-15, Volume: 48Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection.
AID1916552Inhibition of recombinant human ACE2 assessed as maximum inhibition using 7- Mca-YVADAPK (Dnp) as substrate by fluorescence plate reader assay relative to control2021Bioorganic & medicinal chemistry, 10-15, Volume: 48Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection.
AID1916551Inhibition of recombinant human ACE assessed as maximum inhibition using Mca-RPGFSAFK (Dnp)-OH as substrate by fluorescence plate reader assay relative to control2021Bioorganic & medicinal chemistry, 10-15, Volume: 48Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection.
AID1916555Inhibition of ACE in human MNCs assessed as maximum inhibition using substrate Mca-RPGFSAFK (Dnp)-OH as substrate by fluorescence plate reader assay relative to control2021Bioorganic & medicinal chemistry, 10-15, Volume: 48Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection.
AID1798090CPA Inhibition Assay from Article 10.1021/ja0277226: \\Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.\\2002Journal of the American Chemical Society, Oct-09, Volume: 124, Issue:40
Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.
AID1798089Enzyme Inhibition Assay from Article 10.1021/ja0277226: \\Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.\\2002Journal of the American Chemical Society, Oct-09, Volume: 124, Issue:40
Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.
AID1345437Human Angiotensin-converting enzyme 2 (M2: Angiotensin-converting (ACE and ACE2))2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Development of potent and selective phosphinic peptide inhibitors of angiotensin-converting enzyme 2.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (33)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's11 (33.33)29.6817
2010's15 (45.45)24.3611
2020's7 (21.21)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.40

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 Index25.40 (24.57)
Research Supply Index3.56 (2.92)
Research Growth Index4.64 (4.65)
Search Engine Demand Index24.72 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.40)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews2 (5.88%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other32 (94.12%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]