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AC1903

Alias: AC1903; AC-1903; AC 1903;
Cat No.:V10018 Purity: ≥98%
AC1903 is a selective and specific inhibitor of TRPC5 with podocyte protective properties.
AC1903
AC1903 Chemical Structure CAS No.: 831234-13-0
Product category: TRP Channel
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
AC1903 is a selective and specific inhibitor of TRPC5 with podocyte protective properties. AC1903 has no effect on TRPC4 or TRPC6 current and showed no off-target effects in kinase profiling. AC1903 suppresses severe proteinuria and prevents podocyte loss in a rat model of focal segmental glomerulosclerosis (FSGS).
Biological Activity I Assay Protocols (From Reference)
ln Vitro
The brain and kidney have high expression levels of TRPC5, a non-selective cation channel that is permeable to Ca2+. Even in patch-clamp electrophysiological investigations, AC1903 (0-100 µM) suppresses riluzole-activated TRPC5 whole-cell currents, but not carbachol (CCh)-induced TRPC4 or OAG-induced TRPC6 currents. At high micromolar quantities, this is also true. ML204 (IC50=13.6 μM) and AC1903 (IC50=14.7 μM) exhibit nearly comparable ICIC50 values in human embryonic kidney 293 (HEK-293) cells that express TRPC5 [1]. When applied to both wild-type podocytes and podocytes expressing a mutant angiotensin II type 1 (AT1) receptor that is not inactivatable, AC1903 (30 µM) reduces the formation of reactive oxygen species (ROS) generated by angiotensin II[1]. AC1903 (30 µM) inhibits the production of ROS by caAT1R. Within 36 hours of caAT1R expression, there was an increase in podocyte death; however, AC1903 prevented podocytes from dying [1].
ln Vivo
In an AT1 receptor transgenic nephropathy rat model, AC1903 (ip; 50 mg/kg; twice daily; 7 days) effectively suppresses proteinuria and decreases pseudocyst development and podocyte loss [1]. When administered intraperitoneally twice daily at a dose of 50 mg/kg, commencing on day 7 and continuing for one week until day 14, AC1903 significantly reduced proteinuria and preserved the number of podocytes. Furthermore, AC1903 had no effect on blood urea nitrogen, creatinine, or body weight in Dahl S rats, nor did it alter mean arterial pressure (MAP) [1].
Cell Assay
Cell Viability Assay[1]
Cell Types: Podocytes Cell
Tested Concentrations: 30 µM
Incubation Duration: 36 hrs (hours)
Experimental Results: Rescue of podocyte death.
Animal Protocol
Animal/Disease Models: Dahl salt-sensitive rat hypertension-induced focal segmental glomerulosclerosis (FSGS) model [1]
Doses: 50 mg/kg
Route of Administration: intraperitoneal (ip) injection; intraperitoneal (ip) injection. 50 mg/kg; twice (two times) daily; 7 days
Experimental Results: Inhibits progression of proteinuric nephropathy by sparing podocytes.

Animal/Disease Models: 6weeks old Dahl S rats were treated with 2% NaCl for 1 week and suffered from severe and progressive proteinuria [1].
Doses: 50 mg/kg.
Route of Administration: intraperitoneal (ip) injection; intraperitoneal (ip) injection; intraperitoneal (ip) injection. 50 mg/kg; twice (two times) daily; starting on day 7, treatment for 1 week until day 14
Experimental Results: Taking it at the beginning of a high-salt diet diminished the incidence of proteinuria, taking it one week after starting a high-salt diet prevented progression .
References

[1]. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models. Science.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C19H17N3O
Molecular Weight
303.357784032822
Exact Mass
303.137
Elemental Analysis
C, 75.23; H, 5.65; N, 13.85; O, 5.27
CAS #
831234-13-0
PubChem CID
667146
Appearance
Off-white to light yellow solid powder
Density
1.2±0.1 g/cm3
Boiling Point
512.4±60.0 °C at 760 mmHg
Flash Point
263.7±32.9 °C
Vapour Pressure
0.0±1.3 mmHg at 25°C
Index of Refraction
1.648
LogP
4.23
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
5
Heavy Atom Count
23
Complexity
372
Defined Atom Stereocenter Count
0
SMILES
N1=C(NCC2=CC=CO2)N(CC2C=CC=CC=2)C2C1=CC=CC=2
InChi Key
OECUWHDVQIITIS-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H17N3O/c1-2-7-15(8-3-1)14-22-18-11-5-4-10-17(18)21-19(22)20-13-16-9-6-12-23-16/h1-12H,13-14H2,(H,20,21)
Chemical Name
1-benzyl-N-(furan-2-ylmethyl)benzimidazol-2-amine
Synonyms
AC1903; AC-1903; AC 1903;
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~329.64 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (8.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.2964 mL 16.4821 mL 32.9641 mL
5 mM 0.6593 mL 3.2964 mL 6.5928 mL
10 mM 0.3296 mL 1.6482 mL 3.2964 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • AC1903, a specific TRPC5 small-molecule inhibitor, protects podocytes from ROS-mediated injury.
  • AC1903 suppresses proteinuric kidney disease progression and rescues podocytes in AT1R Tg rats with advanced disease.
  • AC1903 suppresses proteinuric kidney disease progression and rescues podocytes in hypertensive Dahl S rats.
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