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

AC1903 

Cat. No.: HY-122051 Purity: 98.64%
Handling Instructions

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.

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

AC1903 Chemical Structure

AC1903 Chemical Structure

CAS No. : 831234-13-0

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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].

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].

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.

831234-13-0

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 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (329.64 mM; Need ultrasonic)

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
10 mM 0.3296 mL 1.6482 mL 3.2964 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 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

  • 2.

    Add each solvent one by one:  10% DMSO    90% corn oil

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

*All of the co-solvents are provided by MCE.
References
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Keywords:

AC1903AC 1903AC-1903TRP ChannelTransient receptor potential channelsfocal segmentalglomerulosclerosisFSGSHEK-293rosTRP channel proteinuriapodocyte losskidney diseaseInhibitorinhibitorinhibit

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