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EC 3.4.23.46 (memapsin 2) inhibitor
An EC 3.4.23.* (aspartic endopeptidase) inhibitor that interferes with the activity of memapsin 2 (EC 3.4.23.46).
ChEBI ID: 74925
Members (6)
| Member | Definition | Class |
|---|---|---|
| carbobenzoxyvalylphenylalanine aldehyde | A dipeptide resulting from the formal condensation of the carboxy group of N-benzyloxycarbonyl-L-valine with the amino group of L-phenylalanine aldehyde. It is a potent cell-permeable inhibitor of calpain I and II, and is also a gamma-secretase inhibitor. | Z-Val-Phe-H |
| l 685458 | A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease. | L-685,458 |
| loganin | An iridoid monoterpenoid with formula C17H26O10 that is isolated from several plant species and exhibits neuroprotective and anti-inflammatory properties. | loganin |
| ly 411575 | A dibenzoazepine that is 5,7-dihydro-6H-dibenzo[b,d]azepin-6-one which is substituted at the 7 pro-S position by the C-terminal carboxamide nitrogen of N(2)-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]-L-alaninamide. It is a potent, cell permeable and selective gamma-secretase inhibitor. It has been tested as a possible treatment for Alzheimer's disease and shows promise for its potential to counteract severe hearing loss. | LY-411575 |
| n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester | A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor. | DAPT |
| ro 4929097 | A member of the class of dibenzoazepines that is the amide formed from formal condensation of the carboxy group of 2,2-dimethyl-3-oxo-3-[(2,2,3,3,3-pentafluoropropyl)amino]propanoic acid with the amino group of (7S)-7-amino-5,7-dihydrodibenzo[b,d]azepin-6-one. | RO4929097 |
Research
Studies (582)
| Timeframe | Studies, Drugs with This Role(%) | All Drugs % |
|---|---|---|
| pre-1990 | 2 (0.34) | 18.7374 |
| 1990's | 5 (0.86) | 18.2507 |
| 2000's | 153 (26.29) | 29.6817 |
| 2010's | 354 (60.82) | 24.3611 |
| 2020's | 68 (11.68) | 2.80 |
Study Types
| Publication Type | Studies, Drugs with this Role (%) | All Drugs (%) |
|---|---|---|
| Trials | 1 (0.16%) | 5.53% |
| Reviews | 20 (3.16%) | 6.00% |
| Case Studies | 1 (0.16%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 611 (96.52%) | 84.16% |
Protein Targets (56)
Potency Measurements
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Drugs |
|---|---|---|---|---|---|
| aldehyde dehydrogenase 1 family, member A1 | Homo sapiens (human) | Potency | 22.3872 | 1 | 1 |
| arylsulfatase A | Homo sapiens (human) | Potency | 2.3934 | 1 | 1 |
| Bloom syndrome protein isoform 1 | Homo sapiens (human) | Potency | 0.0004 | 2 | 2 |
| Chain A, Cruzipain | Trypanosoma cruzi | Potency | 0.0316 | 2 | 2 |
| cytochrome P450 2C9 precursor | Homo sapiens (human) | Potency | 39.8107 | 1 | 1 |
| cytochrome P450 3A4 isoform 1 | Homo sapiens (human) | Potency | 6.3096 | 2 | 3 |
| D(1A) dopamine receptor | Homo sapiens (human) | Potency | 2.0595 | 1 | 1 |
| DNA polymerase eta isoform 1 | Homo sapiens (human) | Potency | 0.2818 | 1 | 1 |
| estrogen-related nuclear receptor alpha | Homo sapiens (human) | Potency | 15.5686 | 3 | 3 |
| euchromatic histone-lysine N-methyltransferase 2 | Homo sapiens (human) | Potency | 41.4568 | 1 | 2 |
| EWS/FLI fusion protein | Homo sapiens (human) | Potency | 18.3397 | 4 | 5 |
| GABA theta subunit | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-1 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-2 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-3 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-4 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-5 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-6 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit beta-1 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit beta-2 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit beta-3 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit delta | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit epsilon | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit gamma-1 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit gamma-2 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit gamma-3 | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit pi | Rattus norvegicus (Norway rat) | Potency | 6.3096 | 1 | 2 |
| geminin | Homo sapiens (human) | Potency | 14.1254 | 1 | 1 |
| Histamine H2 receptor | Cavia porcellus (domestic guinea pig) | Potency | 39.8107 | 1 | 3 |
| histone acetyltransferase KAT2A isoform 1 | Homo sapiens (human) | Potency | 35.4813 | 1 | 1 |
| lamin isoform A-delta10 | Homo sapiens (human) | Potency | 18.8541 | 2 | 2 |
| M-phase phosphoprotein 8 | Homo sapiens (human) | Potency | 56.2341 | 1 | 1 |
| muscarinic acetylcholine receptor M1 | Rattus norvegicus (Norway rat) | Potency | 0.0141 | 1 | 1 |
| NFKB1 protein, partial | Homo sapiens (human) | Potency | 1.7783 | 2 | 2 |
| nuclear receptor ROR-gamma isoform 1 | Mus musculus (house mouse) | Potency | 11.2322 | 2 | 2 |
| peripheral myelin protein 22 isoform 1 | Homo sapiens (human) | Potency | 10.6910 | 1 | 1 |
| TDP1 protein | Homo sapiens (human) | Potency | 34.3044 | 2 | 2 |
| thioredoxin reductase | Rattus norvegicus (Norway rat) | Potency | 0.5012 | 1 | 1 |
| thyroid hormone receptor beta isoform a | Homo sapiens (human) | Potency | 1.5849 | 1 | 1 |
| vitamin D3 receptor isoform VDRA | Homo sapiens (human) | Potency | 70.7946 | 1 | 1 |
Inhibition Measurements
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Drugs |
|---|---|---|---|---|---|
| 5-hydroxytryptamine receptor 1B | Rattus norvegicus (Norway rat) | IC50 | 0.3000 | 1 | 1 |
| Beta-secretase 1 | Homo sapiens (human) | IC50 | 0.3000 | 1 | 1 |
| Beta-secretase 2 | Homo sapiens (human) | IC50 | 0.3000 | 1 | 1 |
| Calpain-1 catalytic subunit | Homo sapiens (human) | IC50 | 0.3000 | 1 | 1 |
| Calpain-1 catalytic subunit | Homo sapiens (human) | Ki | 0.0080 | 1 | 1 |
| Calpain-1 catalytic subunit | Sus scrofa (pig) | Ki | 0.0100 | 1 | 1 |
| Cathepsin B | Homo sapiens (human) | Ki | 0.0240 | 1 | 1 |
| Chymotrypsinogen A | Bos taurus (cattle) | Ki | 54.0000 | 1 | 1 |
| Gamma-secretase subunit APH-1A | Homo sapiens (human) | IC50 | 5.6875 | 14 | 18 |
| Gamma-secretase subunit APH-1B | Homo sapiens (human) | IC50 | 5.6875 | 14 | 18 |
| Gamma-secretase subunit PEN-2 | Homo sapiens (human) | IC50 | 5.4040 | 15 | 19 |
| Nicastrin | Homo sapiens (human) | IC50 | 5.6875 | 14 | 18 |
| Presenilin-1 | Homo sapiens (human) | IC50 | 5.6875 | 14 | 18 |
| Presenilin-2 | Homo sapiens (human) | IC50 | 5.6875 | 14 | 18 |
| Replicase polyprotein 1ab | Severe acute respiratory syndrome coronavirus 2 | IC50 | 20.0000 | 1 | 1 |
| Signal peptide peptidase-like 2A | Homo sapiens (human) | IC50 | 0.0100 | 1 | 1 |
| Signal transducer and activator of transcription 3 | Homo sapiens (human) | IC50 | 14.0000 | 1 | 1 |
Activation Measurements
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Drugs |
|---|---|---|---|---|---|
| Gamma-secretase subunit APH-1A | Homo sapiens (human) | EC50 | 0.0064 | 3 | 3 |
| Gamma-secretase subunit APH-1B | Homo sapiens (human) | EC50 | 0.0064 | 3 | 3 |
| Gamma-secretase subunit PEN-2 | Homo sapiens (human) | EC50 | 0.0064 | 3 | 3 |
| Nicastrin | Homo sapiens (human) | EC50 | 0.0064 | 3 | 3 |
| Presenilin-1 | Homo sapiens (human) | EC50 | 0.0039 | 5 | 5 |
| Presenilin-2 | Homo sapiens (human) | EC50 | 0.0064 | 3 | 3 |
Other Measurements
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Drugs |
|---|---|---|---|---|---|
| Gamma-secretase subunit PEN-2 | Homo sapiens (human) | ED50 | 0.0250 | 2 | 2 |