Disease relevance of SC 39026

• Failure to inhibit medial hypertrophy with SC-39026 suggests that a different mechanism or a different elastase may be involved in this structural change [1].
• SC-39026 did not significantly reduce monocrotaline-induced medial hypertrophy of muscular arteries, endothelial injury, and associated subendothelial edema; nor was there a significant increase in the proportion of the medial elastin, although a trend was apparent [1].
• SC-39026 is inactive against hog pancreatic elastase, bovine alpha-chymotrypsin and Pseudomonas aeruginosa elastase, but does inhibit human neutrophil cathepsin G with an IC50 of approximately 2.5 microM [2].
• SC-39026 reduced the number of muscularized arteries and the level of pulmonary arterial pressure during exposure to chronic hypoxia [3].
• Our previous studies showed that increased pulmonary artery elastolytic activity is associated with monocrotaline-induced pulmonary hypertension in rats, and the latter is reduced by the elastase inhibitor SC-39026 [4].

High impact information on SC 39026

• In contrast, monocrotaline-injected rats given SC-39026 had significantly lower mean pulmonary artery pressure than those given vehicle (21.0 +/- 1.6 vs. 27.5 +/- 0.8 mm Hg, p less than 0.05), and this correlated with a significant reduction in the number of abnormally muscularized arteries at alveolar wall level (r2 = 0.89, p less than 0.001) [1].
• ICI-200,880, a competitive slow-binding elastase inhibitor, was significantly less potent to inhibit A alpha(1-21), having an IC50 of 75 microM, while Declaben, a reversible noncompetitive inhibitor, was inactive at concentrations as great as 200 microM [5].
• SC-39026, (+/-) 2-chloro-4-(1-hydroxyoctadecyl)benzoic acid, inhibits human neutrophil elastase with an IC50 of 0.5 microM (KI of 1.5 microM) [2].
• Neutrophil elastases isolated from rat, hamster, rabbit and hog are also inhibited by SC-39026 [2].
• Previously in rats injected with the toxin monocrotaline and administered SC-39026, a serine elastase inhibitor, pulmonary hypertension was decreased in association with reduced muscularization of peripheral pulmonary arteries [3].

Gene context of SC 39026

• SC-39026, a specific human neutrophil elastase inhibitor [2].
• To further assess whether the protective effect of SC-39026 was related to its inhibition of elastase, an extended study was carried out using a different elastase inhibitor, alpha 1-proteinase inhibitor [3].

References