AC1903

SKU: orb1220049

Description

AC1903 is a specific inhibitor of TRPC5 channel, and has been shown to suppress severe proteinuria and prevent podocyte loss.AC1903, that 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. TRPC5 activity drives disease and that TRPC5 inhibitors may be valuable for the treatment of progressive kidney diseases.

Key Properties

• CAS Number: 831234-13-0
• MW: 303.36
• Purity: >98% (HPLC)
• Formula: C₁₉H₁₇N₃O
• SMILES: C(NC1=NC2=CC=CC=C2N1CC1=CC=CC=C1)C1=CC=CO1
• Target: TRP/TRPV Channel
• Solubility: In Vitro: DMSO : 100 mg/mL (329.64 mM)

Bioactivity

• 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. 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. Animal model: Hypertension-induced focal segmental glomerulosclerosis (FSGS) model in Dahl salt-sensitive rats. 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. 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.
• 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. 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 (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. Cell Viability Assay Cell line: Podocyte cells. Concentration: 30 μM. Incubation time: 36 hours. Result: Rescued podocyte cell death.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

TRP/TRPV Channel