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AC1903

Cat. No. M10318
AC1903 Structure
Synonym:

AC-1903

Size Price Availability Quantity
10mg USD 102  USD102 In stock
25mg USD 220  USD220 In stock
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Quality Control & Documentation
Biological Activity

AC1903 is a specific inhibitor of TRPC5 channel. AC1903 does no effects on TRPC4 or TRPC6 currents and shows no off-target effects in kinase profiling assays. AC1903 (30 µM) inhibits angiotensin II-induced production of reactive oxygen species (ROS) in wild-type podocytes and podocytes expressing a mutant angiotensin II type 1 (AT1) receptor that cannot be inactivated and endocytosed. 

AC1903 specifically blocks TRPC5 channel activity in glomeruli of proteinuric rats. Chronic administration of AC1903 suppressed severe proteinuria and prevented podocyte loss in a transgenic rat model of FSGS. AC1903 also provided therapeutic benefit in a rat model of hypertensive proteinuric kidney disease.

Chemical Information
Molecular Weight 303.36
Formula C19H17N3O
CAS Number 831234-13-0
Solubility (25°C) DMSO ≥ 60 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Swagat H Sharma, et al. Bioorg Med Chem Lett. Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

[2] Yiming Zhou, et al. Science. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models

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