1. Membrane Transporter/Ion Channel Neuronal Signaling
  2. TRP Channel
  3. AC1903

AC1903 is a specific and selective inhibitor of TRPC5 and has podocyte-protective properties. AC1903 does no effects on TRPC4 or TRPC6 currents and shows no off-target effects in kinase profiling assays. AC1903 suppresses severe proteinuria and prevents podocyte loss in focal segmental glomerulosclerosis (FSGS) rat model.

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AC1903 Chemical Structure

AC1903 Chemical Structure

CAS No. : 831234-13-0

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10 mM * 1 mL in DMSO
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Based on 1 publication(s) in Google Scholar

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1 Publications Citing Use of MCE AC1903

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Description

AC1903 is a specific and selective inhibitor of TRPC5 and has podocyte-protective properties. AC1903 does no effects on TRPC4 or TRPC6 currents and shows no off-target effects in kinase profiling assays. AC1903 suppresses severe proteinuria and prevents podocyte loss in focal segmental glomerulosclerosis (FSGS) rat model[1].

IC50 & Target

IC50: 14.7 μM (TRPC5 current IN HEK-293 cells)[1]

In Vitro

TRPC5 is a Ca2+ permeable nonselective cation channel highly expressed in brain and kidney.
AC1903 (0-100 µM) blocks riluzole-activated TRPC5 whole-cell current, but fails to block carbachol (CCh)–induced TRPC4 and OAG-induced TRPC6 currents, even at high micromolar concentrations in Patch-clamp electrophysiology experiments. The ICIC50 values of ML204 (HY-12949) (IC50=13.6 μM) and AC1903 (IC50=14.7 μM) are nearly equipotent in human embryonic kidney 293 (HEK-293) cells expressing TRPC5[1].
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[1].
AC1903 (30 µM) blocks caAT1R-induced ROS generation. Increased podocyte cell death within 36 hours of caAT1R expression is observed, but AC1903  protects podocyte cells from cell death[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: Podocyte cells
Concentration: 30 µM
Incubation Time: 36 hours
Result: Rescued podocyte cell death.
In Vivo

AC1903 (intraperitoneal injection; 50 mg/kg; twice per day; 7 days) significantly suppresses proteinuria as well as reduces pseudocyst formation and podocyte loss in an AT1 receptor transgenic rat model of kidney disease[1].
AC1903 (intraperitoneal injection; 50 mg/kg; twice per day; initiated on day 7 and treated for 1 week until day 14) initiatation on day 7 exhibits significant suppression of proteinuria with preserved podocyte numbers. Besides, AC1903 does not affect the mean arterial pressure (MAP) and exhibits no effect on body weight, blood urea nitrogen, or creatinine in Dahl S rats[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Hypertension-induced focal segmental glomerulosclerosis (FSGS) model in Dahl salt-sensitive rats[1]
Dosage: 50 mg/kg
Administration: Intraperitoneal injection; 50 mg/kg; twice per day; 7 days
Result: Inhibited the progression of proteinuric kidney disease by preserving podocytes.
Animal Model: 6-week-old Dahl S rats received 2% NaCl for 1 week with severe, progressive proteinuric disease[1]
Dosage: 50 mg/kg
Administration: Intraperitoneal injection; 50 mg/kg; twice per day; initiated on day 7 and treated for 1 week until day 14
Result: Decreased the rate of proteinuria when administered at the beginning of a high-salt diet and prevents progression when administered one week following initiation of a high-salt diet.
Molecular Weight

303.36

Formula

C19H17N3O

CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

C1(NCC2=CC=CO2)=NC3=CC=CC=C3N1CC4=CC=CC=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (329.64 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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  • Dilution Calculator

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (8.24 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (8.24 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.90%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.2964 mL 16.4821 mL 32.9641 mL 82.4103 mL
5 mM 0.6593 mL 3.2964 mL 6.5928 mL 16.4821 mL
10 mM 0.3296 mL 1.6482 mL 3.2964 mL 8.2410 mL
15 mM 0.2198 mL 1.0988 mL 2.1976 mL 5.4940 mL
20 mM 0.1648 mL 0.8241 mL 1.6482 mL 4.1205 mL
25 mM 0.1319 mL 0.6593 mL 1.3186 mL 3.2964 mL
30 mM 0.1099 mL 0.5494 mL 1.0988 mL 2.7470 mL
40 mM 0.0824 mL 0.4121 mL 0.8241 mL 2.0603 mL
50 mM 0.0659 mL 0.3296 mL 0.6593 mL 1.6482 mL
60 mM 0.0549 mL 0.2747 mL 0.5494 mL 1.3735 mL
80 mM 0.0412 mL 0.2060 mL 0.4121 mL 1.0301 mL
100 mM 0.0330 mL 0.1648 mL 0.3296 mL 0.8241 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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AC1903
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