TRC4186
TRC4186 is a potent advanced glycation end-product (AGE) breaker. TRC4186 breaks advanced glycation end-products, reduces their tissue accumulation, and decreases AGE burden. TRC4186 improves endothelial and myocardial function, preserves cardiac function, retards renal dysfunction, and reduces renal dysfunction severity. TRC4186 downregulates brain natriuretic peptide and IL-6 expression. TRC4186 can be used for the research of diabetic macro- and microvascular complications, diabetic heart failure, diabetic renal failure, hypertension, diabetes, diabetic cardiomyopathy, and diabetic nephropathy.
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- CAS. Nr.: 357625-50-4
- Formel: C13H14ClN3O4S2
- Molecular Weight:375.85
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
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IL-6 |
TRC4186, an AGE-breaker, decreases AGE burden in in vitro systems[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
TRC4186 (9-27 mg/kg; i.p.; twice daily; 34 weeks) dose-dependently preserves cardiac function, reduces blood pressure, lowers cardiac inflammatory and dysfunction markers, and at 27 mg/kg, reduces the severity of renal dysfunction in Ob-ZSF1 rats with type 2 diabetes and associated cardiomyopathy and nephropathy[3].
TRC4186 improves diabetic cardiomyopathy and nephropathy in obese Zucker spontaneously hypertensive fatty rats, a model of type 2 diabetes with hypertension[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Ob-ZSF1 (male, 12-13 weeks old at study initiation, type 2 diabetes with diabetic cardiomyopathy and nephropathy model, 0.5% salt added to drinking water from week 29 to accelerate vasculopathy)[3]
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Dosage:9 mg/kg; 27 mg/kg
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Administration:i.p.; twice daily; 34 weeks
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Result:Prevented a significant rise in systolic and diastolic blood pressure from baseline over 34 weeks, with systolic blood pressure significantly reduced compared to baseline up to week 17 and no significant rise at week 34 (27 mg/kg group).
Improved cardiac output significantly compared to controls (27 mg/kg group).
Shortened the time constant of left ventricular pressure decay (ζ) to 15.38 msec vs. 19.18 msec in controls (27 mg/kg group).
Lowered minimum diastolic pressure to 0.69 mmHg vs. 1.29 mmHg in controls (27 mg/kg group).
Reduced the slope of the end diastolic pressure volume relationship (EDPVR) to 0.079 mmHg/μL vs. 0.118 mmHg/μL in controls (27 mg/kg group).
Reduced peripheral resistance to 0.034 mmHg/mL/min/100 gm vs. 0.084 mmHg/mL/min/100 gm in controls (27 mg/kg group).
Reduced end systolic volume significantly (27 mg/kg group).
Increased preload recruitable stroke work by 23% compared to controls (27 mg/kg group).
Reduced brain natriuretic peptide (BNP) expression to 0.48 vs. 1.13 in controls (27 mg/kg group).
Reduced interleukin-6 (IL-6) expression to 1.24 vs. 3.24 in controls (27 mg/kg group).
Reduced relative heart wet weight to 0.296 g per 100 g body weight vs. 0.342 g per 100 g body weight in controls (27 mg/kg group).
Increased frequency of mild (grade 1) myocardial lesions to 87% vs. 13% in controls and reduced severe lesions (27 mg/kg group).
Reduced advanced glycation end product (AGE) labeling in aorta (27 mg/kg group).
Reduced percent increases from baseline in urinary albumin excretion, urine creatinine excretion, and albumin-to-creatinine ratio over 8 months (27 mg/kg group).
Reduced severity of glomerulosclerosis, tubular atrophy, and interstitial inflammation compared to controls (27 mg/kg group).
Improved cardiac output significantly compared to controls (9 mg/kg group).
Increased end diastolic volume significantly (9 mg/kg group).
Reduced the slope of the EDPVR to 0.074 mmHg/μL vs. 0.118 mmHg/μL in controls (9 mg/kg group).
Reduced peripheral resistance by 50% to 0.037 mmHg/mL/min/100 gm vs. 0.084 mmHg/mL/min/100 gm in controls (9 mg/kg group).
Increased end systolic volume significantly compared to controls (9 mg/kg group).
Increased preload recruitable stroke work by 16% compared to controls (9 mg/kg group).
Reduced BNP expression to 0.99 vs. 1.13 in controls (9 mg/kg group).
Reduced IL-6 expression to 1.26 vs. 3.24 in controls (9 mg/kg group).
Showed no significant improvement in renal function compared to controls (9 mg/kg group).
Chemical Information
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CAS. Nr. 357625-50-4
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Molecular Weight 375.85
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Formel C13H14ClN3O4S2
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SMILES
O=C(C1=CC=C[N+](CC(C2=CC=CS2)=O)=C1)NNS(=O)(C)=O.[Cl-]
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Chandra KP, Shiwalkar A, Kotecha J, Thakkar P, Srivastava A, Chauthaiwale V, Sharma SK, Cross MR, Dutt C. Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects. Clinical drug investigation. 2009 Sep;29(9):559-75. [Content Brief]
[2]. Rosenthal T, et al. Combating Combination of Hypertension and Diabetes in Different Rat Models. Pharmaceuticals (Basel, Switzerland). 2010 Mar 26;3(4):916-939. [Content Brief]
[3]. Joshi D, et al. TRC4186, a novel AGE-breaker, improves diabetic cardiomyopathy and nephropathy in Ob-ZSF1 model of type 2 diabetes. Journal of cardiovascular pharmacology. 2009 Jul;54(1):72-81. [Content Brief]
[4]. Yamagishi S, et al. Potential clinical utility of advanced glycation end product cross-link breakers in age- and diabetes-associated disorders. Rejuvenation research. 2012 Dec;15(6):564-72. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
TRC4186 Related Classifications
HY-171336 Related Classifications
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