Literature summary for 3.4.21.35 extracted from

Sexton, D.J.; Chen, T.; Martik, D.; Kuzmic, P.; Kuang, G.; Chen, J.; Nixon, A.E.; Zuraw, B.L.; Forteza, R.M.; Abraham, W.M.; Wood, C.R.
Specific inhibition of tissue kallikrein 1 with a human monoclonal antibody reveals a potential role in airway diseases (2009), Biochem. J., 422, 383-392.

Search for more literature for 3.4.21.35

Activating Compound

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

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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Mus musculus	-	-	-
Ovis aries	-	-	-

Source Tissue

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 and Products (Substrate)

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

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 [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

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Release 2023.1 (January 2023)