SM19712 free acid
SM19712 free acid is an orally active, selective endothelin converting enzyme (ECE) inhibitor. SM19712 free acid inhibits conversion of big ET-1 to ET-1. SM19712 free acid attenuates colonic angiogenesis, tissue injury, inflammation, without altering colon shortening or myeloperoxidase levels in mice. SM19712 free acid can be used for the research of inflammatory bowel disease (colitis), ischemic acute renal failure, acute myocardial infarction, and myocardial ischemia/reperfusion injury.
For research use only. We do not sell to patients.
- CAS No.: 194542-49-9
- Formula: C18H14ClN5O3S
- Molecular Weight:415.85
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
SM19712 free acid potently inhibits ECE solubilized from rat lung microsomes with an IC50 of 42 nM[3].
SM19712 (10-300 μM) free acid shows high specificity for ECE, with no significant inhibitory activity against NEP, ACE, 13 tested receptors, or 9 tested enzymes at concentrations up to 300 μM[3].
SM19712 (1-100 μM; 6 h) free acid concentration-dependently inhibits endogenous ET-1 production in cultured porcine aortic endothelial cells with an IC50 of 31 μM[3].
SM19712 (100 μM) free acid exhibits high selectivity for endothelin-converting enzyme, with minimal inhibitory effects on neutral endopeptidase, angiotensin converting enzyme, collagenase IV, and other proteinase classes[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
SM19712 (3-30 mg/kg; i.v.; single bolus 5 minutes before occlusion) dose-dependently attenuates ischemia/reperfusion-induced acute renal failure in Sprague-Dawley rats[2].
SM19712 (0.3-30 mg/kg; i.v.; single dose) free acid dose-dependently suppresses Big ET-1-induced pressor responses in rats[3].
SM19712 (10-30 mg/kg; p.o.; single dose) free acid significantly suppresses big ET-1-induced pressor responses in rats by 37.2%[3].
SM19712 (25.9 mg/kg bolus, 1.7 mg/kg/min infusion; i.v.; single bolus followed by continuous infusion; duration of experiment) free acid significantly reduces infarct size, serum ET-1 elevation, and serum CPK activity in a rabbit model of acute myocardial infarction induced by coronary occlusion and reperfusion[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice (~28 g; inflammatory bowel disease induced by 5% 40 kD Dextran Sodium Sulfate (DDS) in drinking water for 5-6 days)[1]
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Dosage:15 mg/kg/day
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Administration:p.o.; daily; 5-6 days
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Result:Attenuated DSS-induced increases in colonic ET-1 immunostaining.
Reduced DSS-induced PECAM-1 immunostaining.
Attenuated DSS-induced histologic injury and inflammation.
Decreased the incidence of loose stools and fecal blood.
Reduced DSS-induced weight loss.
Significantly decreased the overall disease activity index in DSS-treated mice.
Did not significantly affect DSS-induced colon shortening or tissue myeloperoxidase activity.
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Animal Model:Sprague-Dawley rats (male, 10 weeks old, 280-300 g, acute renal failure induced by right nephrectomy 2 weeks prior followed by 45-minute left renal artery and vein occlusion then reperfusion)[2]
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Dosage:3; 10; 30 mg/kg
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Administration:i.v.; single bolus 5 minutes before occlusion
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Result:Reduced BUN, increased creatinine clearance, reduced urine flow, increased urinary osmolality, and reduced fractional excretion of sodium.
Attenuated tubular necrosis grade, proteinaceous casts grade, and medullary congestion grade.
Reduced renal ET-1 content.
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Animal Model:Sprague-Dawley rats (male, 300-400 g, anesthetized, ganglionic-blocked, challenged with Big Edothelin-1)[3]
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Dosage:0.3; 1; 3; 10; 30 mg/kg
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Administration:i.v.; single dose
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Result:Dose-dependently suppressed the pressor response induced by Big ET-1.
Significantly reduced the pressor response.
Had no effect on baseline pressure or the pressor response induced by mature ET-1.
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Animal Model:Sprague-Dawley rats (male, 280-400 g, conscious then anesthetized, challenged with big endothelin-1)[3]
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Dosage:10; 30 mg/kg
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Administration:p.o.; single dose
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Result:Produced a 37.2% suppression of the big ET-1-induced pressor response at 30 mg/kg.
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Animal Model:New Zealand White rabbits (male, 2.6-3.5 kg, subjected to 30 minutes of coronary artery occlusion followed by 5 hours of reperfusion)[3]
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Dosage:25.9 mg/kg (bolus); 1.7 mg/kg/min (continuous infusion)
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Administration:i.v.; single bolus followed by continuous infusion; duration of experiment
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Result:Significantly reduced myocardial infarct size, expressed as a percentage of both the left ventricle area and the area at risk, compared to vehicle.
Significantly attenuated the increase in serum ET-1 concentration and serum CPK activity seen in vehicle-treated rabbits during reperfusion.
Chemical Information
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CAS No. 194542-49-9
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Molecular Weight 415.85
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Formula C18H14ClN5O3S
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SMILES
O=S(C1=CC=C(C=C1)Cl)(NC(NC2=C(C(C)=NN2C3=CC=CC=C3)C#N)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Lee S, et al. Effects of the endothelin-converting enzyme inhibitor SM-19712 in a mouse model of dextran sodium sulfate-induced colitis. Inflamm Bowel Dis. 2009 Jul;15(7):1007-13. [Content Brief]
[2]. Matsumura Y, et al. Protective effect of SM-19712, a novel and potent endothelin converting enzyme inhibitor, on ischemic acute renal failure in rats. Jpn J Pharmacol. 2000 Sep;84(1):16-24. [Content Brief]
[3]. Umekawa K, et al. Pharmacological characterization of a novel sulfonylureid-pyrazole derivative, SM-19712, a potent nonpeptidic inhibitor of endothelin converting enzyme. Jpn J Pharmacol. 2000 Sep;84(1):7-15. [Content Brief]
[4]. Tawa M, et al. Role of endogenous endothelin-1 in post-ischemic cardiac dysfunction and norepinephrine overflow in rat hearts. Eur J Pharmacol. 2008 Sep 4;591(1-3):182-8. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SM19712 free acid Related Classifications
HY-120148 Related Classifications
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- SM19712
- 194542-49-9
- SM 19712
- SM-19712
- Endothelin-Converting Enzyme (ECE)
- Endothelin Receptor
- endothelin converting enzyme
- ischemic acute renal failure
- rat lung microsomes
- inflammatory bowel disease
- acute myocardial infarction
- human middle meningeal arteries
- Sprague-Dawley rats
- porcine aortic endothelial cells
- human coronary arteries
- C57BL/6 mice
- Inhibitor
- inhibitor
- inhibit