Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | exposure of tracheobronchial epithelial cells to reactive oxygen species results in a significant increase in the amount of active KLK1 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
4-(2-aminoethyl)benzenesulfonyl fluoride | is an active-site-directed covalent inhibitor | Homo sapiens | |
D-Pro-Phe-Arg-chloromethane | is an active-site-directed covalent inhibitor | Homo sapiens | |
DX-2300 | DX-2300 is a fully human antibody that inhibits KLK1 via a competitive inhibition mechanism. Completely inhibits KLK1-like activity in urine and saliva, inhibits KLK1-like activity by 70% in bronchoalveolar lavage fluid. Inability of DX-2300 to bind either KLK1 covalently modified with 4-(2-aminoethyl)benzenesulfonyl fluoride or D-Pro-Phe-Arg-chloromethane, thus DX-2300 binds at or near the active site of the enzyme. DX-2300 blocks oxidative-stress-induced epidermal-growth-factor receptor activation and downstream mucus cell proliferation and hypersecretion, which is mediated by KLK1. DX-2300 is a potent and specific inhibitor of KLK1 that is efficacious in in vitro and in vivo models of airway disease | Homo sapiens | |
DX-2300 | completely inhibits KLK1-like activity in urine. In an allergic sheep model of asthma, inhalation of either 1 or 5 mg of DX-2300 inhibits high-molecular mass kininogen-induced bronchoconstriction by 49 and 68%, respectively | Ovis aries | |
additional information | DX-2300 is a fully human antibody, it does not inhibit the KLK1-like activity in mouse urine | Mus musculus |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Ovis aries | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
blood plasma | - |
Homo sapiens | - |
bronchoalveolar lavage fluid | - |
Homo sapiens | - |
saliva | - |
Homo sapiens | - |
serum | - |
Homo sapiens | - |
tracheobronchial epithelial cell | - |
Homo sapiens | - |
urine | - |
Mus musculus | - |
urine | - |
Homo sapiens | - |
urine | - |
Ovis aries | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
Pro-Phe-Arg-7-amido-4-methylcoumarin + H2O | - |
Mus musculus | Pro-Phe-Arg + 7-amino-4-methylcoumarin | - |
? | |
Pro-Phe-Arg-7-amido-4-methylcoumarin + H2O | - |
Homo sapiens | Pro-Phe-Arg + 7-amino-4-methylcoumarin | - |
? | |
Pro-Phe-Arg-7-amido-4-methylcoumarin + H2O | - |
Ovis aries | Pro-Phe-Arg + 7-amino-4-methylcoumarin | - |
? | |
Val-Leu-Arg-4-nitroanilide + H2O | tracheobronchial epithelial cells grown at the air/liquid interface | Homo sapiens | Val-Leu-Arg + 4-nitroaniline | - |
? |
Synonyms | Comment | Organism |
---|---|---|
KLK1 | - |
Mus musculus |
KLK1 | - |
Homo sapiens |
KLK1 | - |
Ovis aries |
tissue kallikrein 1 | - |
Mus musculus |
tissue kallikrein 1 | - |
Homo sapiens |
tissue kallikrein 1 | - |
Ovis aries |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00000013 | - |
DX-2300 | in 20 mM Tris/HCl buffer, pH 7.5, 150 mM NaCl, 1 mM EDTA, 0.1% poly(ethylene glycol)-8000 and 0.1% Triton X-100 | Homo sapiens |