Compounds > kmi-420
Page last updated: 2024-12-11

kmi-420

Description

KMI-420: a protease inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID6918784
CHEMBL ID183494
MeSH IDM0483977

Synonyms (6)

Synonym
kmi-420
bdbm50157439
3-((2r,3s)-3-((s)-2-((s)-2-((s)-2-amino-3-(2h-tetrazole-5-carboxamido)propanamido)-3-methylbutanamido)-4-methylpentanamido)-2-hydroxy-4-phenylbutanamido)benzoic acid
3-{(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}-benzoic acid
CHEMBL183494 ,
3-[(2h-tetrazol-5-ylcarbonyl)amino]-l-alanyl-l-valyl-n-((1s,2r)-1-benzyl-3-[(3-carboxyphenyl)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)0.00820.00061.619410.0000AID241188; AID264166; AID314585; AID317231; AID550164; 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 (15)

Assay IDTitleYearJournalArticle
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.
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.
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.
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.
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.
AID268731Inhibition of human recombinant BACE1 at 0.2 uM2006Bioorganic & medicinal chemistry letters, Aug-15, Volume: 16, Issue:16
beta-Secretase inhibitors: modification at the P4 position and improvement of inhibitory activity in cultured cells.
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.
AID550164Inhibition of BACE12011Bioorganic & medicinal chemistry, Jan-01, Volume: 19, Issue:1
Investigation of α-phenylnorstatine and α-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors.
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.
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.
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.
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.
AID317231Inhibition of BACE12008Bioorganic & medicinal chemistry letters, Mar-01, Volume: 18, Issue:5
BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety.
AID268730Inhibition of human recombinant BACE1 at 2 uM2006Bioorganic & medicinal chemistry letters, Aug-15, Volume: 16, Issue:16
beta-Secretase inhibitors: modification at the P4 position and improvement of inhibitory activity in cultured cells.
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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (9)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's5 (55.56)29.6817
2010's4 (44.44)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: 38.81

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index38.81 (24.57)
Research Supply Index2.30 (2.92)
Research Growth Index4.37 (4.65)
Search Engine Demand Index53.49 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (38.81)

All Compounds (24.57)

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%
Other9 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
thiazoles
[no description available]		2.05101,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		2.05101,2,3-triazole
kmi-429
KMI-429: 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
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