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Cat. No.: HY-187638

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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.

For research use only. We do not sell to patients.

CAS No.: 192511-71-0
Formula: C₅H₁₄ClN₅O
Molecular Weight:195.65

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

ALT-946 Chemical Structure

CAS No.: 192511-71-0

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- In Vitro
- In Vivo
Chemical Information
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Biological Activity

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 (0.03-10 mg/kg; p.o.; daily; 8 weeks) is a potent inhibitor of in vivo AGE-protein cross-linking, with 0.03 mg/kg daily oral dosing normalizing RBC-IgG levels in Streptozotocin (HY-13753)-induced diabetic Lewis rats^[1].
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.

Animal Model:

Lewis rats (male, ~200 g, streptozotocin-induced diabetic)^[1]
Dosage:

0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration:

p.o.; daily; 8 weeks
Result:

Normalized RBC-IgG levels completely in diabetic rats at 0.03 mg/kg.

Animal Model:

Sprague Dawley rats (male, 200-250 g, streptozotocin-induced diabetic)^[1]
Dosage:

1 g/L (continuous 32 weeks); 1 g/L (delayed 16 weeks)
Administration:

p.o.; daily; 32 weeks; p.o.; daily; 16 weeks (delayed from week 16 to 32)
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.

Animal Model:

(mREN-2)27 (female, 6 weeks old, streptozotocin-induced diabetic nephropathy)^[3]
Dosage:

1 g/L
Administration:

p.o.; daily; 12 weeks
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.

Animal Model:

(mREN-2)27 (female, 6 weeks old)^[3]
Dosage:

1 g/L
Administration:

p.o.; daily; 12 weeks
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

CAS No. 192511-71-0
Molecular Weight 195.65
Formula C₅H₁₄ClN₅O
SMILES

O=C(C)NCCNC(NN)=N.Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Forbes JM, et al. Renoprotective effects of a novel inhibitor of advanced glycation. Diabetologia. 2001 Jan;44(1):108-14. [Content Brief]

[2]. Thomas MC, et al. The role of AGEs and AGE inhibitors in diabetic cardiovascular disease. Current drug targets. 2005 Jun;6(4):453-74.

[3]. Wilkinson-Berka JL, et al. ALT-946 and aminoguanidine, inhibitors of advanced glycation, improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat. Diabetes. 2002 Nov;51(11):3283-9.

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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100 mg

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