ALT-946
ALT-946 is an orally active inhibitor of the advanced glycation end product (AGE) formation pathway. ALT-946 blocks the formation of AGE-protein cross-links, reduces the accumulation of AGE in renal tissues, alleviates increased albuminuria and elevated glomerular filtration rate, prevents glomerulosclerosis, ameliorates medullary tubulointerstitial lesions, and reduces cortical tubular degeneration. ALT-946 can be used in research related to diabetic nephropathy and diabetic cardiovascular diseases.
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- CAS No.: 192511-71-0
- Formule: C5H14ClN5O
- Masse moléculaire:195.65
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
Description
In Vitro
ALT-946 (0.1-30.0 mM) potently inhibits AGE-BSA cross-linking to rat tail tendon collagen in vitro with an IC50 of 3.4 mM[1].
ALT-946 potently inhibits AGE-protein cross-linking in an in vitro purified protein system[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ALT-946 (1 g/L; p.o.; daily; 32 weeks or 16 weeks delayed) confers renoprotective effects in streptozotocin-induced diabetic Sprague Dawley rats, including attenuation of hyperfiltration, prevention of albuminuria, and inhibition of glomerular AGE accumulation[1].
ALT-946 (1 g/L; p.o.; daily; 12 weeks) confers renoprotection in hypertensive transgenic (mREN-2)27 rats with streptozotocin-induced diabetic nephropathy, reducing albumin excretion rate by 250%, normalizing glomerulosclerosis, improving medullary pathology, and reducing cortical tubular degeneration and renal AGE accumulation without altering blood pressure[3].
ALT-946 (1 g/L; p.o.; daily; 12 weeks) has no measurable effect on renal function, histopathology, or AGE levels in healthy nondiabetic transgenic (mREN-2)27 rats[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Lewis rats (male, ~200 g, streptozotocin-induced diabetic)[1]
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Dosage:0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 8 weeks
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Result:Normalized RBC-IgG levels completely in diabetic rats at 0.03 mg/kg.
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Animal Model:Sprague Dawley rats (male, 200-250 g, streptozotocin-induced diabetic)[1]
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Dosage:1 g/L (continuous 32 weeks); 1 g/L (delayed 16 weeks)
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Administration:p.o.; daily; 32 weeks; p.o.; daily; 16 weeks (delayed from week 16 to 32)
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Result:Did not affect body weight, glycaemic control, or systolic blood pressure in diabetic rats.
Attenuated the diabetes-associated increase in glomerular filtration rate.
Prevented the development of diabetes-associated albuminuria.
Reduced glomerular AGE staining to levels similar to non-diabetic control rats.
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Animal Model:(mREN-2)27 (female, 6 weeks old, streptozotocin-induced diabetic nephropathy)[3]
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Dosage:1 g/L
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Administration:p.o.; daily; 12 weeks
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Result:Reduced the diabetes-induced increase in albumin excretion rate by 250%.
Lowered glomerulosclerotic index to nondiabetic control levels.
Improved medullary tubulointerstitial collagen deposition to a similar extent as aminoguanidine.
Reduced cortical tubular degeneration to a greater degree than aminoguanidine, lowering the number of degenerated tubules per field compared to untreated diabetic rats.
Reduced increased glomerular and tubulointerstitial AGE immunolabeling in diabetic rats to near nondiabetic levels.
Did not alter diabetes-induced increases in kidney weight or glomerular filtration rate.
Did not affect systolic blood pressure or body weight in either nondiabetic or diabetic rats.
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Animal Model:(mREN-2)27 (female, 6 weeks old)[3]
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Dosage:1 g/L
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Administration:p.o.; daily; 12 weeks
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Result:Showed no effect on body weight, kidney weight, systolic blood pressure, glomerular filtration rate, or albumin excretion rate.
Did not alter renal histology, glomerulosclerotic index, cortical tubular morphology, or AGE immunolabeling, all remaining consistent with untreated nondiabetic controls.
Chemical Information
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CAS No. 192511-71-0
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Masse moléculaire 195.65
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Formule C5H14ClN5O
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SMILES
O=C(C)NCCNC(NN)=N.Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ALT-946 Related Classifications
HY-187638 Related Classifications
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Keywords
- ALT-946
- 192511-71-0
- ALT946
- ALT 946
- Biochemical Assay Reagents
- rat tail tendon collagen
- diabetic cardiovascular disease
- streptozotocin-induced diabetic Lewis rats
- renal tissues
- diabetic nephropathy
- glomerulosclerosis
- advanced glycation end-product
- albuminuria
- glomerular filtration rate
- nitric oxide synthase
- Inhibitor
- inhibitor
- inhibit