Uses
BAY 678, is a human neutrophil elastase (HNE) inhibitor with >2,000-fold selectivity for HNE over a panel of 21 other serine proteases.
Biological Activity
bay-678 is an orally active, potent and selective inhibitor of human neutrophil elastase (hne) [1][2].human neutrophil elastase (hne) is a member of the chymotrypsin-like family of serine proteases and is stored in the neutrophil cytoplasm. hne is a key protease for matrix degradation and high hne activity is occured in inflammatory diseases. so hne is a potential target for the treatment of pulmonary diseases such as acute lung injury (ali), acute respiratory distress syndrome (ards), chronic obstructive pulmonary disease (copd), bronchiectasis (be), and pulmonary hypertension (ph) [1].bay-678 is an orally active, potent and selective inhibitor of human neutrophil elastase (hne). bay-678 inhibited hne reversibly with ic50 value of 20 nm and ki value of 15 nm. bay-678 showed no inhibition against 21 related serine proteases, up to a concentration of 30 μm [1].in rats, bay-678 showed medium clearance with t1/2 of 1.3h [1].
Biochem/physiol Actions
BAY-678 is an orally available, highly potent and selective inhibitor of human neutrophil elastase (HNE). For full characterization details, please visit the BAY-678 probe summary on the Structural Genomics Consortium (SGC) website.BAY-677 is used as a negative control and is available from Sigma. To learn more about and purchase BAY-677, click here.To learn about other SGC chemical probes for protein targets, visit sigma.com/sgc
in vivo
BAY-678 (17) reveals significant efficacy in preclinical models of ALI and lung emphysema, demonstrating their anti-inflammatory and anti-remodeling mode of action. Additionally, BAY-678 (17) has shown significant beneficial pulmonary hemodynamic and vascular effects in models of PAH in rats and mice[2].
References
[1]. von nussbaum f, li vm, allerheiligen s, et al. freezing the bioactive conformation to boost potency: the identification of bay 85-8501, a selective and potent inhibitor of human neutrophil elastase for pulmonary diseases. chemmedchem. 2015 jul;10(7):1163-73.
[2]. von nussbaum f, li vm, meibom d, et al. potent and selective human neutrophil elastase inhibitors with novel equatorial ring topology: in vivo efficacy of the polar pyrimidopyridazine bay-8040 in a pulmonary arterial hypertension rat model. chemmedchem. 2016 jan 19;11(2):199-206.
