Crystallization (Comment) | Organism |
---|---|
- |
Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
4-fluoro-N-prop-2-yn-1-yl-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | - |
Homo sapiens | |
E-64 | - |
Homo sapiens | |
additional information | irreversible covalent inhibitors can have a beneficial pharmacokinetic/pharmacodynamics profile but are still often avoided due to the risk of indiscriminate ovalent reactivity and the resulting adverse effects. To overcome this potential liability, we introduced an alkyne moiety as a latent electrophile into small molecule inhibitors of cathepsin K (CatK). Alkyne-based inhibitors do not show indiscriminate thiol reactivity but potently inhibit CatK protease activity by formation of an irreversible covalent bond with the catalytic cysteine residue. Binding mode of alkynes is irreversible and covalent | Homo sapiens | |
N-(1-ethynylcyclopropyl)-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | - |
Homo sapiens | |
N-(3-bromoprop-2-yn-1-yl)-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | - |
Homo sapiens | |
N-(cyanomethyl)-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | - |
Homo sapiens | |
N-but-3-yn-2-yl-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | - |
Homo sapiens | |
odanacatib | - |
Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P43235 | - |
- |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
osteoclast | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O | - |
Homo sapiens | benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin | - |
? |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00000056 | - |
50 mM MES pH 5.5, 25 mM EDTA and 2.5 mM DTT. 0.05% Tween20 (v/v), 37°C | Homo sapiens | odanacatib | |
0.00000057 | - |
50 mM MES pH 5.5, 25 mM EDTA and 2.5 mM DTT. 0.05% Tween20 (v/v), 37°C | Homo sapiens | N-(cyanomethyl)-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | |
0.0000019 | - |
pH and temperature not specified in the publication | Homo sapiens | E-64 | |
0.000047 | - |
50 mM MES pH 5.5, 25 mM EDTA and 2.5 mM DTT. 0.05% Tween20 (v/v), 37°C | Homo sapiens | N-(3-bromoprop-2-yn-1-yl)-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | |
0.00029 | - |
50 mM MES pH 5.5, 25 mM EDTA and 2.5 mM DTT. 0.05% Tween20 (v/v), 37°C | Homo sapiens | 4-fluoro-N-prop-2-yn-1-yl-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | |
0.00035 | - |
50 mM MES pH 5.5, 25 mM EDTA and 2.5 mM DTT. 0.05% Tween20 (v/v), 37°C | Homo sapiens | N-but-3-yn-2-yl-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide | |
0.026 | - |
50 mM MES pH 5.5, 25 mM EDTA and 2.5 mM DTT. 0.05% Tween20 (v/v), 37°C | Homo sapiens | N-(1-ethynylcyclopropyl)-4-fluoro-N2-[(1S)-2,2,2-trifluoro-1-[4'-(methanesulfonyl)[1,1'-biphenyl]-4-yl]ethyl]-L-leucinamide |