| Description |
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 (Ki=0.0168 nM) than for rat (Ki=3 nM), mouse (Ki=1.8 nM), and rabbit (Ki= 58 nM) elastases[2].
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| Related Catalog |
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| In Vitro |
SSR69071 is a potent inhibitor of human leukocyte elastase (HLE), with the inhibition constant (Ki) and the constant for inactivation process (kon) 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 Ki value of 16.8 pM[3].
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| 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]. Animal Model: Male New Zealand white rabbits weighing 2-3 kg[1] Dosage: 3 mg/kg (dissolved in methane sulphonic acid before being diluted in 0.9% saline) Administration: Administered i.v. Result: Treatment just prior to reperfusion significantly reduced cardiac elastase activity.
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| References |
[1]. Jean-Pierre Bidouard, et al. SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia-reperfusion injury. Eur J Pharmacol. 2003 Feb 7;461(1):49-52. [2]. Zoltan Kapui, et al. Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor. J Pharmacol Exp Ther. 2003 May;305(2):451-9. [3]. Márton Varga, et al. A novel orally active inhibitor of HLE. Eur J Med Chem. 2003 Apr;38(4):421-5.
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