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Literature summary extracted from
- Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein (2008), J. Biol. Chem., 283, 7745-7753.
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 3.4.22.1 | medicine | cathepsin B inhibitors are effective therapeutic agents in treatment of Alzheimer's disease reducing the amyloid beta plaque load in brain regions by up to 55%, reducing the formation of amyloid beta 40 and amyloid beta 42 by 45% and 40%, and improving the memory function, overview | Mus musculus |
| 3.4.23.46 | pharmacology | treatment of London APP transgenic mouse model of Alzheimer's disease that expresses human amyloid precursor protein containing the wild-type beta-secretase site with inhibitors CA074Me or E64d results in substantial improvement in memory deficit assessed by the Morris water maze test. Improved memory function is accompanied by reduced amyloid plaque load, decreased amyloid beta40 and amyloid beta42, and reduced C-terminal beta-secretase fragment derived from amyloid precursor protein by beta-secretase. Inhibitor hHas no effects on any of these parameters in mice expressing the Swedish mutant beta-secretase site of amyloid precursor protein | Mus musculus |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.4.22.1 | additional information | inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein | Mus musculus |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.22.1 | E64c | - |
Mus musculus |  |
| 3.4.22.1 | E64d | - |
Mus musculus | |
| 3.4.22.1 | N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline | i.e. CA074 | Mus musculus | |
| 3.4.22.1 | N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline methyl ester | i.e. CA074Me | Mus musculus | |
| 3.4.23.46 | CA074Me | treatment of London APP transgenic mouse model of Alzheimer's disease that expresses human amyloid precursor protein containing the wild-type beta-secretase site results in substantial improvement in memory deficit assessed by the Morris water maze test. Improved memory function is accompanied by reduced amyloid plaque load, decreased amyloid beta40 and amyloid beta42, and reduced C-terminal beta-secretase fragment derived from amyloid precursor protein by beta-secretase. Inhibitor has no effects on any of these parameters in mice expressing the Swedish mutant beta-secretase site of amyloid precursor protein | Mus musculus | |
| 3.4.23.46 | E64d | treatment of London APP transgenic mouse model of Alzheimer's disease that expresses human amyloid precursor protein containing the wild-type beta-secretase site results in substantial improvement in memory deficit assessed by the Morris water maze test. Improved memory function is accompanied by reduced amyloid plaque load, decreased amyloid beta40 and amyloid beta42, and reduced C-terminal beta-secretase fragment derived from amyloid precursor protein by beta-secretase. Inhibitor has no effects on any of these parameters in mice expressing the Swedish mutant beta-secretase site of amyloid precursor protein | Mus musculus | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 3.4.22.1 | secretory vesicle | regulated | Mus musculus | 99503 | - |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.4.22.1 | amyloid beta precursor protein + H2O | Mus musculus | cathepsin B selectively cleaves the wild-type beta-secretase site but not the rare Swedish mutant beta-secretase site | ? | - |
? | |
| 3.4.22.1 | additional information | Mus musculus | inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.4.22.1 | Mus musculus | - |
London APP mice and C57BL/6 mice | - |
| 3.4.23.46 | Mus musculus | - |
- |
- |
| 3.4.23.46 | Mus musculus | - |
London APP transgenic mouse model of Alzheimer's disease that expresses human amyloid precursor protein containing the wild-type beta-secretase site | - |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 3.4.22.1 | brain | - |
Mus musculus | - |
| 3.4.22.1 | hippocampus | - |
Mus musculus | - |
| 3.4.22.1 | additional information | two mouse models of Alzheimer's Disease, consisting of one expressing human amyloid precursor protein containing the wild-type beta-secretase site and mutation at the beta-secretase site, London amyloid precursor protein mice, and the other expressing the Swe mutant beta-secretase site and the London mutation, Swedish/London amyloid precursor protein | Mus musculus | - |
| 3.4.23.46 | brain | - |
Mus musculus | - |
Specific Activity [micromol/min/mg]
| EC Number | Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|---|
| 3.4.23.46 | 0.01 | - |
using Z-Val-Asn-Leu-7-amido-4-methylcoumarin as substrate | Mus musculus |
| 3.4.23.46 | 0.02 | - |
- |
Mus musculus |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.4.22.1 | amyloid beta precursor protein + H2O | cathepsin B selectively cleaves the wild-type beta-secretase site but not the rare Swedish mutant beta-secretase site | Mus musculus | ? | - |
? | |
| 3.4.22.1 | additional information | inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein | Mus musculus | ? | - |
? | |
| 3.4.22.1 | N-benzoyl-Val-Asn-Leu-7-amido-4-methylcoumarin + H2O | the substrate represents the wild-type beta-secretase site | Mus musculus | N-benzoyl-Val-Lys-Met + 7-amino-4-methylcoumarin | - |
? | |
| 3.4.22.1 | N-benzoyl-Val-Lys-Met-7-amido-4-methylcoumarin + H2O | the substrate represents the wild-type beta-secretase site | Mus musculus | N-benzoyl-Val-Lys-Met + 7-amino-4-methylcoumarin | - |
? | |
| 3.4.23.46 | additional information | BACE 1 does not cleave Z-Val-Lys-Met-7-amido-4-methylcoumarin | Mus musculus | ? | - |
? | |
| 3.4.23.46 | Z-Val-Asn-Leu-7-amido-4-methylcoumarin + H2O | - |
Mus musculus | Z-Val-Asn-Leu + 7-amino-4-methylcoumarin | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.4.23.46 | BACE 1 | - |
Mus musculus |
| 3.4.23.46 | beta-secretase | - |
Mus musculus |
IC50 Value
| EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|---|
| 3.4.22.1 | 0.0000003 | - |
- |
Mus musculus | E64c | |
| 3.4.22.1 | 0.000002 | - |
- |
Mus musculus | N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline | |
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