| Field | Specification |
|---|---|
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C19H17N3O |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
AC1903 is a specific, selective inhibitor of TRPC5 with podocyte-protective properties. It has no effect on TRPC4 or TRPC6 currents and shows no off-target effects in kinase profiling assays. In a focal segmental glomerulosclerosis (FSGS) rat model, it suppresses severe proteinuria and prevents podocyte loss[1]. It is supplied as an off-white to light yellow solid (C19H17N3O, MW 303.36) at 99.69% purity.
Physical & Chemical Properties
| CAS Number | 831234-13-0 |
|---|---|
| Molecular Formula | C19H17N3O |
| Molecular Weight | 303.36 g/mol |
| Purity | 99.69% |
| Appearance | Solid |
| Color | Off-white to light yellow |
| SMILES | C1(NCC2=CC=CO2)=NC3=CC=CC=C3N1CC4=CC=CC=C4 |
| Signaling Pathway | Membrane Transporter/Ion Channel; Neuronal Signaling |
| Solubility | In Vitro: DMSO: 100 mg/mL (329.64 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 2 years; -20°C, 1 year. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
IC50: 14.7 μM (TRPC5 current IN HEK-293 cells)[1]
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 100 mg/mL (329.64 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 2 years) or -20°C (up to 1 year); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 2.5 mg/mL (8.24 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 2
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 2.5 mg/mL (8.24 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
TRPC5 is a Ca2+ permeable nonselective cation channel that is highly expressed in brain and kidney. In patch-clamp electrophysiology experiments, AC1903 (0-100 μM) blocks riluzole-activated TRPC5 whole-cell current but does not block carbachol (CCh)-induced TRPC4 or OAG-induced TRPC6 currents, even at high micromolar concentrations. In human embryonic kidney 293 (HEK-293) cells expressing TRPC5, ML204 (IC50=13.6 μM) and AC1903 (IC50=14.7 μM) are nearly equipotent[1]. AC1903 (30 μM) inhibits production of reactive oxygen species (ROS) induced by angiotensin II in wild-type podocytes and in podocytes that express a mutant form of the angiotensin II type 1 (AT1) receptor, one that cannot be inactivated or endocytosed[1]. AC1903 (30 μM) blocks caAT1R-induced ROS generation. Podocyte cell death rises within 36 hours of caAT1R expression, but AC1903 protects the podocytes from this death[1].
Cell Viability Assay[1]
| Cell Line | Podocyte cells |
|---|---|
| Concentration | 30 μM |
| Incubation Time | 36 hours |
| Result | Rescued podocyte cell death. |
In Vivo
In an AT1 receptor transgenic rat model of kidney disease, AC1903 (intraperitoneal injection; 50 mg/kg; twice per day; 7 days) significantly lowers proteinuria and reduces pseudocyst formation and podocyte loss[1]. When AC1903 (intraperitoneal injection; 50 mg/kg; twice per day; started on day 7 and given for 1 week until day 14) is used, proteinuria is significantly suppressed and podocyte numbers are preserved. In Dahl S rats, AC1903 also leaves the mean arterial pressure (MAP) unchanged and has no effect on body weight, blood urea nitrogen, or creatinine[1].
| 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. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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Delineating Zinc Influx Mechanisms during Platelet Activation. Int J Mol Sci 2023 Jul 20;24(14):11689. PMID: 37511448
