Application | Comment | Organism |
---|---|---|
pharmacology | design of inhibitor drugs for treatment of Alzheimer disease | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
conformational study of BACE1 inhibitor, molecular surface model and stereoview indicated | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2-[[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]carbamoyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridin-4-yl methanesulfonate | i.e. KMI-1036, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | |
3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3,5-di-2H-tetrazol-5-ylphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide | i.e. KMI-684, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized | Homo sapiens | |
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 | i.e. KMI-429, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized | Homo sapiens | |
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 | i.e. KMI-420, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized | Homo sapiens | |
3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-[(1S,2R)-1-benzyl-2-hydroxy-3-oxo-3-([3-(2H-tetrazol-5-yl)phenyl]amino)propyl]-L-leucinamide | i.e. KM-570, beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere, inihbitory activities optimized | Homo sapiens | |
additional information | isophthalic-type aromatic residues at the P2 position and an HMC isostere at the P1 position used as lead compounds for generation of novel inhibitors against beta-secretase BACE1, development of novel inhibitors against beta-secretase BACE1 studied, novel nonpeptidic and small-sized BACE1 inhibitors possessing a 2,6-pyridinedicarboxylic, chelidamic or chelidonic residue at the P2 position described, inhibitory activities summarized | Homo sapiens | |
N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-1,4-dihydropyridine-2-carboxamide | i.e. KMI-1030, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | |
N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-4H-pyran-2-carboxamide | i.e. KMI-1027, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | |
N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridine-2-carboxamide | i.e. KMI-1023, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P56817 | - |
- |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
additional information | - |
synthesis, structure and potencies of BACE1 inhibitors shown, inhibitory assays summarized, novel nonpeptidic and small-sized BACE1 inhibitors developed, design of small-sized BACE1 inhibitor 2 possessing heterocyclic ring at the P2 position shown, reagents and conditions summarized, BACE1 inhibitors possessing benzylamino-type groups at the P3 position and their BACE1 inhibitory activities summarized, BACE1 inhibitors with a 5-membered ring at the P3 position and inhibitory activities indicated, molecular surface properties shown | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | synthesis, structure and potencies of beta-secretase BACE1 inhibitors optimized, in vivo enzymatic stability and permeability across the blood-brain barrier of penta-peptidic inhibitors analyzed, stereoview and molecular surface properties shown, reagents and conditions summarized | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
BACE1 | - |
Homo sapiens |
beta-secretase | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
additional information | - |
beta-secretase inhibitors with a hydroxymethylcarbonyl (HMC) isostere used as a substrate transition-state mimic, potent BACE1 inhibitory activities of about 0.0012 mM IC50 shown, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | additional information | |
0.0012 | - |
i.e. KMI-684, used as a substrate transition-state mimic | Homo sapiens | 3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-((1S,2R)-1-benzyl-3-[(3,5-di-2H-tetrazol-5-ylphenyl)amino]-2-hydroxy-3-oxopropyl)-L-leucinamide | |
0.0039 | - |
i.e. KMI-429, used as a substrate transition-state mimic | Homo sapiens | 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 | |
0.0048 | - |
i.e. KMI-570, used as a substrate transition-state mimic | Homo sapiens | 3-[(2H-tetrazol-5-ylcarbonyl)amino]-L-alanyl-L-valyl-N-[(1S,2R)-1-benzyl-2-hydroxy-3-oxo-3-([3-(2H-tetrazol-5-yl)phenyl]amino)propyl]-L-leucinamide | |
0.0082 | - |
i.e. KMI-420, used as a substrate transition-state mimic | Homo sapiens | 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 | |
0.05 | - |
i.e. KMI-1027, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-4H-pyran-2-carboxamide | |
0.096 | - |
i.e. KMI-1036, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | 2-[[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]carbamoyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridin-4-yl methanesulfonate | |
0.14 | - |
i.e. KMI-1023, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]pyridine-2-carboxamide | |
0.36 | - |
i.e. KMI-1030, BACE1 inhibitors with a 5-membered ring at the P3 position and their BACE1 inhibitory activities summarized | Homo sapiens | N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxo-3-[[3-(2H-tetrazol-5-yl)phenyl]amino]propyl]-4-oxo-6-[[(4S)-4-phenyl-1,3-oxazolidin-3-yl]carbonyl]-1,4-dihydropyridine-2-carboxamide |