Aliskiren hemifumarate

SKU: orb1225938

Description

The first in a class, potent and highly selective, direct renin inhibitor with IC50 of 0.6 nM; no significant inhibition on Cathepsin D, Cathepsin E, Pepsin and HIV-1 peptidase (> 50 uM); orally bioactive.Hypertension Approved(In Vitro):Aliskiren hemifumarate inhibits plasma renin activity (PRA) in vitro with IC50s of 2.9 nM (human PRA), 8.0 nM (monkey PRA), respectively.Aliskiren hemifumarate (5 μM; 24 h) inhibits prorenin-induced human aortic smooth muscle cell migration.Aliskiren hemifumarate (1-10 μM; 24 h) inhibits both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity.(In Vivo):Aliskiren hemifumarate (3 mg/kg, 10 mg/kg; p.o.; daily; 0-12 d) inhibit renin and lower blood pressure without affecting heart rate in sodium-depleted marmosets.Aliskiren hemifumarate (10 mg/kg; p.o.; single dose) delays cachexia development, reduces tumor, and prolongs mouse survival. And also improves whole body strength, mobility and coordination, enhances locomotor activity, and inhibits muscle wasting.Aliskiren hemifumarate (10 mg/kg; p.o.; single dose; 20 d after C26 injection) reduces oxidative stress associated with cancer cachexia.

Key Properties

• CAS Number: 173334-58-2
• MW: 1219.589
• Purity: >98% (HPLC)
• Formula: C₆₄H₁₁₀N₆O₁₆
• SMILES: CC(C)[C@@H](CC1=CC(=C(C=C1)OC)OCCCOC)C[C@@H]([C@H](C[C@@H](C(C)C)C(=O)NCC(C)(C)C(=O)N)O)N.CC(C)[C@@H](CC1=CC(=C(C=C1)OC)OCCCOC)C[C@@H]([C@H](C[C@@H](C(C)C)C(=O)NCC(C)(C)C(=O)N)O)N.C(=C/C(=O)O)\C(=O)O
• Target: Renin
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Aliskiren hemifumarate (3 mg/kg, 10 mg/kg; p.o. ; daily; 0-12 d) inhibit renin and lower blood pressure without affecting heart rate in sodium-depleted marmosets. Aliskiren hemifumarate (10 mg/kg; p.o. ; single dose) delays cachexia development, reduces tumor, and prolongs mouse survival. And also improves whole body strength, mobility and coordination, enhances locomotor activity, and inhibits muscle wasting. Aliskiren hemifumarate (10 mg/kg; p.o. ; single dose; 20 d after C26 injection) reduces oxidative stress associated with cancer cachexia. Animal model: Sodium-depleted marmosets. Dosage: 3 mg/kg, 10 mg/kg. Administration: Oral gavage; once daily; 12 days. Result: Increased plasma immunoreactive renin levels, and lowered blood pressure without affecting heart rate. Showed no rebound increase in BP following the end of treatment with either dose of aliskiren. Inhibited the RAS and controls the upregulation of pro inflammatory cytokines. Animal model: Cancer cachexia model in BALB/c mice injected with C26 mouse colon carcinoma cells. Dosage: 10 mg/kg. Administration: Oral gavage; on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection; for 20 days after C26 injection. Result: Enhanced grip strength, coordination, and locomotor activity. Inhibited serum Ang I and Ⅱ levels and both serum and muscular tumor necrosis factor α (TNF α) and inter leukin 6 (IL 6) levels.
• In Vitro:
  Aliskiren hemifumarate inhibits plasma renin activity (PRA) in vitro with IC50s of 2.9 nM (human PRA), 8.0 nM (monkey PRA), respectively. Aliskiren hemifumarate (5 μM; 24 h) inhibits prorenin-induced human aortic smooth muscle cell migration. Aliskiren hemifumarate (1-10 μM; 24 h) inhibits both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity. Cell Viability Assay Cell line: Smooth muscle cell (SMC). Concentration: 1-10 μM. Incubation time: 24 hours. Result: Inhibited human aortic smooth muscle cell migration induced by prorenin (10 nM) at 10 μM.

Storage & Handling

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

Alternative Names

CGP 60536 | CGP60536B | SPP 100

Quick Database Links

Gene Symbol

Renin