SSR69071

SSR69071 is a potent, orally active and selective inhibitor of neutrophil elastase. SSR69071 reduces myocardial infarct size following ischemia-reperfusion injury^[1]. SSR69071 displays a higher affinity for human elastase (K_i=0.0168 nM) than for rat (K_i=3 nM), mouse (K_i=1.8 nM), and rabbit (K_i= 58 nM) elastases^[2]. In Vitro: SSR69071 is a potent inhibitor of human leukocyte elastase (HLE), with the inhibition constant (K_i) and the constant for inactivation process (k_on) being 0.0168±0.0014 nM and 0.183±0.013 10⁶/mol sr, respectively^[2].
SSR69071 is a potent, competitive and slow tight binding inhibitor of HLE in vitro with a K_i value of 16.8 pM^[3]. In Vivo: SSR69071 (3 mg/kg i.v.) reduces cardiac infarct size when administered before ischemia or just prior to reperfusion^[1].

Treatment with SSR69071 (3 mg/kg i.v.) just prior to reperfusion significantly reduces cardiac elastase activity^[1].
Bronchoalveolar lavage fluid from mice orally treated with SSR69071 inhibits HLE (ex vivo), and in this model, SSR69071 has a dose-dependent efficacy with an ED₅₀=10.5 mg/kg p.o. SSR69071 decreases significantly the acute lung hemorrhage induced by HLE (ED₅₀=2.8 mg/kg p.o.) in mice^[2]. SSR69071 prevents carrageenan- (ED₃₀=2.2 mg/kg) and HLE-induced (ED₃₀=2.7 mg/kg) paw edema in rats after p.o. administration^[2].