Compounds > kmi-429
Page last updated: 2024-10-14

kmi-429

Description

KMI-429: a protease inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID6918785
CHEMBL ID183546
SCHEMBL ID14341943
MeSH IDM0483978

Synonyms (8)

Synonym
kmi-429
bdbm50157441
5-{(s)-3-[2-((s)-2-{(2s,3s)-2-amino-3-[(1h-tetrazole-5-carbonyl)-amino]-propionylamino}-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-2-hydroxy-1-(r)-oxo-4-phenyl-butylamino}-isophthalic acid
5-((2r,3s)-3-((s)-2-((s)-2-((s)-2-amino-3-(2h-tetrazole-5-carboxamido)propanamido)-3-methylbutanamido)-4-methylpentanamido)-2-hydroxy-4-phenylbutanamido)isophthalic acid
CHEMBL183546 ,
5-[[(2r,3s)-3-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(2h-tetrazole-5-carbonylamino)propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-2-hydroxy-4-phenylbutanoyl]amino]benzene-1,3-dicarboxylic acid
SCHEMBL14341943
3-[(2h-tetrazol-5-ylcarbonyl)amino]-l-alanyl-l-valyl-n-((1s,2r)-1-benzyl-3-[(3,5-dicarboxyphenyl)amino]-2-hydroxy-3-oxopropyl)-l-leucinamide
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Beta-secretase 1Homo sapiens (human)IC50 (µMol)0.00390.00061.619410.0000AID1192278; AID241188; AID264166; AID314585; AID317231; AID614067; AID640217
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (16)

Processvia Protein(s)Taxonomy
proteolysisBeta-secretase 1Homo sapiens (human)
membrane protein ectodomain proteolysisBeta-secretase 1Homo sapiens (human)
response to lead ionBeta-secretase 1Homo sapiens (human)
protein processingBeta-secretase 1Homo sapiens (human)
amyloid-beta formationBeta-secretase 1Homo sapiens (human)
amyloid precursor protein catabolic processBeta-secretase 1Homo sapiens (human)
positive regulation of neuron apoptotic processBeta-secretase 1Homo sapiens (human)
amyloid-beta metabolic processBeta-secretase 1Homo sapiens (human)
detection of mechanical stimulus involved in sensory perception of painBeta-secretase 1Homo sapiens (human)
prepulse inhibitionBeta-secretase 1Homo sapiens (human)
cellular response to copper ionBeta-secretase 1Homo sapiens (human)
cellular response to manganese ionBeta-secretase 1Homo sapiens (human)
presynaptic modulation of chemical synaptic transmissionBeta-secretase 1Homo sapiens (human)
signaling receptor ligand precursor processingBeta-secretase 1Homo sapiens (human)
cellular response to amyloid-betaBeta-secretase 1Homo sapiens (human)
amyloid fibril formationBeta-secretase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (8)

Processvia Protein(s)Taxonomy
amyloid-beta bindingBeta-secretase 1Homo sapiens (human)
endopeptidase activityBeta-secretase 1Homo sapiens (human)
aspartic-type endopeptidase activityBeta-secretase 1Homo sapiens (human)
protein bindingBeta-secretase 1Homo sapiens (human)
peptidase activityBeta-secretase 1Homo sapiens (human)
beta-aspartyl-peptidase activityBeta-secretase 1Homo sapiens (human)
enzyme bindingBeta-secretase 1Homo sapiens (human)
protein serine/threonine kinase bindingBeta-secretase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (20)

Processvia Protein(s)Taxonomy
lysosomeBeta-secretase 1Homo sapiens (human)
endosomeBeta-secretase 1Homo sapiens (human)
early endosomeBeta-secretase 1Homo sapiens (human)
late endosomeBeta-secretase 1Homo sapiens (human)
multivesicular bodyBeta-secretase 1Homo sapiens (human)
endoplasmic reticulum lumenBeta-secretase 1Homo sapiens (human)
Golgi apparatusBeta-secretase 1Homo sapiens (human)
trans-Golgi networkBeta-secretase 1Homo sapiens (human)
plasma membraneBeta-secretase 1Homo sapiens (human)
synaptic vesicleBeta-secretase 1Homo sapiens (human)
cell surfaceBeta-secretase 1Homo sapiens (human)
endosome membraneBeta-secretase 1Homo sapiens (human)
membraneBeta-secretase 1Homo sapiens (human)
axonBeta-secretase 1Homo sapiens (human)
dendriteBeta-secretase 1Homo sapiens (human)
neuronal cell bodyBeta-secretase 1Homo sapiens (human)
membrane raftBeta-secretase 1Homo sapiens (human)
recycling endosomeBeta-secretase 1Homo sapiens (human)
Golgi-associated vesicle lumenBeta-secretase 1Homo sapiens (human)
hippocampal mossy fiber to CA3 synapseBeta-secretase 1Homo sapiens (human)
endosomeBeta-secretase 1Homo sapiens (human)
plasma membraneBeta-secretase 1Homo sapiens (human)
trans-Golgi networkBeta-secretase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (13)

Assay IDTitleYearJournalArticle
AID241188Inhibitory activity against beta-secretase 1 (BACE1)2005Bioorganic & medicinal chemistry letters, Jan-03, Volume: 15, Issue:1
Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.
AID264164Inhibition of BACE1 at 2 uM2006Bioorganic & medicinal chemistry letters, May-01, Volume: 16, Issue:9
Design and synthesis of potent beta-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres.
AID614067Inhibition of BACE12011Bioorganic & medicinal chemistry, Sep-01, Volume: 19, Issue:17
Structure-guided design and synthesis of P1' position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors.
AID243835Inhibitory activity against beta-secretase 1 (BACE1) at 0.2 uM2005Bioorganic & medicinal chemistry letters, Jan-03, Volume: 15, Issue:1
Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.
AID317230Inhibition of human recombinant BACE1 at 0.2 uM2008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety.
AID243826Inhibitory activity against beta-secretase 1 (BACE1) at 2 uM2005Bioorganic & medicinal chemistry letters, Jan-03, Volume: 15, Issue:1
Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.
AID264165Inhibition of BACE1 at 0.2 uM2006Bioorganic & medicinal chemistry letters, May-01, Volume: 16, Issue:9
Design and synthesis of potent beta-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres.
AID317229Inhibition of human recombinant BACE1 at 2 uM2008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety.
AID317231Inhibition of BACE12008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety.
AID314585Inhibition of human recombinant BACE1 by FRET assay2008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
Novel non-peptidic and small-sized BACE1 inhibitors.
AID640217Inhibition of human recombinant BACE1 by FRET assay2012Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2
Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design.
AID1192278Inhibition of BACE1 (unknown origin)2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Novel β-amyloid aggregation inhibitors possessing a turn mimic.
AID264166Inhibition of BACE12006Bioorganic & medicinal chemistry letters, May-01, Volume: 16, Issue:9
Design and synthesis of potent beta-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (8)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's5 (62.50)29.6817
2010's3 (37.50)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%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other8 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
kmi-420
KMI-420: a protease inhibitor; structure in first source		8.2960
ConditionIndicatedRelationship StrengthStudiesTrials
Acute Confusional Senile Dementia
[description not available]		02.0310
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)		02.0310
Protein Aggregation, Pathological
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION; POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.		02.1110