1448314-31-5 Usage
Biological Activity
neutrophil elastase inhibitor is a neutrophil elastase inhibitor.human neutrophil elastase (hne) is a member of the chymotrypsin superfamily of serine proteases that is involved in the response to inflammatory stimuli. hne is reported to be stored in azurophilic granules of neutrophils and is greatly aggressive and cytotoxic, as its substrates include various components of the extracellular matrix.
in vitro
previous study found that neutrophil elastase inhibitor was able to inhibit thrombin and urokinase at micromolar concentrations. in addition, neutrophil elastase inhibitor appeared to be a specific hne inhibitors in a competitive manner. moreoer, the hydrolysis of the acyl-enzyme complex for neutrophil elastase inhibitor was found to be much slower than spontaneous hydrolysis of neutrophil elastase inhibitor, and hne was observed to be still inhibited to 80% of control level at 7 h after treatment [1].
IC 50
7 nm
references
[1] l. crocetti, i. a. schepetkin, a. cilibrizzi, et al. optimization of n-benzoylindazole derivatives as inhibitors of human neutrophil elastase. journal of medicinal chemistry 56(15), 6259-6272 (2013).
Check Digit Verification of cas no
The CAS Registry Mumber 1448314-31-5 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,8,3,1 and 4 respectively; the second part has 2 digits, 3 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1448314-31:
(9*1)+(8*4)+(7*4)+(6*8)+(5*3)+(4*1)+(3*4)+(2*3)+(1*1)=155
155 % 10 = 5
So 1448314-31-5 is a valid CAS Registry Number.
1448314-31-5Relevant articles and documents
Optimization of N-benzoylindazole derivatives as inhibitors of human neutrophil elastase
Crocetti, Letizia,Schepetkin, Igor A.,Cilibrizzi, Agostino,Graziano, Alessia,Vergelli, Claudia,Giomi, Donatella,Khlebnikov, Andrei I.,Quinn, Mark T.,Giovannoni, Maria Paola
, p. 6259 - 6272 (2013/09/02)
Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease selectivity, and stability compared to our previous leads. Introduction of a variety of substituents at position 5 of the indazole resulted in the potent inhibitor 20f (IC50 ～10 nM) and modifications at position 3 resulted the most potent compound in this series, the 3-CN derivative 5b (IC50 = 7 nM); both derivatives demonstrated good stability and specificity for HNE versus other serine proteases. Molecular docking of selected N-benzoylindazoles into the HNE binding domain suggested that inhibitory activity depended on geometry of the ligand-enzyme complexes. Indeed, the ability of a ligand to form a Michaelis complex and favorable conditions for proton transfer between Hys57, Asp102, and Ser195 both affected activity.
