Application | Comment | Organism |
---|---|---|
pharmacology | design of inhibitor drugs for treatment of Alzheimer disease | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
conformational study of BACE1 inhibitor shown, molecular surface model and stereoview indicated | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(2S,5S,8S,11S,14S)-14-amino-5-benzyl-8-(cyclohexylmethyl)-16-(5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-2-hydroxy-11-(1-methylethyl)-4,7,10,13,16-pentaoxo-N-[3-(2H-tetrazol-5-yl)phenyl]-3,6,9,12-tetraazahexadecan-1-amide | i.e. KMI-574, 100% and 97% inhibition at 2 microM and 0.2 microM, respectively, 84% inhibition of beta-secretase BACE1 in cultured cell-based assay at 100 microM | Homo sapiens | |
additional information | structures of BACE1 inhibitors containing a tetrazole ring at the P4 position indicated, inhibitory activities summarized | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P56817 | - |
- |
Purification (Comment) | Organism |
---|---|
SDS-PAGE | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HEK-293 cell | stably expressing human BACE1 enzyme, used for inhibition assay | Homo sapiens | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
additional information | - |
BACE1 inhibitors generated by 9-fluorenylmethoxycarbonyl-solid-phase peptide synthesis methods, characterization of BACE1 inhibitor KMI-574, generation by replacement of acidic tetrazole ring with hydrogen bond acceptor group indicated, potent inhibitory activity in cultured cells as well as in vitro enzymatic assay shown, inhibitory activities summarized | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
((7-methoxycoumarin-4-yl)acetyl)-Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys(2,4-dinitrophenyl)-Arg-Arg-NH2 + H2O | synthesis, structure and potencies of beta-secretase BACE1 inhibitors optimized, effects of P4 modification on BACE1 inhibitory activity analyzed | Homo sapiens | ((7-methoxycoumarin-4-yl)acetyl)-Ser-Glu-Val-Asn-Leu + Asp-Ala-Glu-Phe-Lys(2,4-dinitrophenyl)-Arg-Arg-NH2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
BACE1 | - |
Homo sapiens |
beta-secretase | - |
Homo sapiens |
beta-site APP (amyloid precursor protein) cleaving enzyme | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
cellular inhibition assay at | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0056 | - |
i.e. KMI-574, used as a substrate transition-state mimic | Homo sapiens | (2S,5S,8S,11S,14S)-14-amino-5-benzyl-8-(cyclohexylmethyl)-16-(5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-2-hydroxy-11-(1-methylethyl)-4,7,10,13,16-pentaoxo-N-[3-(2H-tetrazol-5-yl)phenyl]-3,6,9,12-tetraazahexadecan-1-amide |