Aliskiren Hydrochloride

Aliskiren (CGP 60536; CGP60536B; SPP 100) hydrochloride is an orally active and selective renin inhibitor, with IC50 of 1.5 nM. Aliskiren hydrochloride can be used for the research of hypertension, cardiovascular diseases and cancer cachexia[1]-[4].

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Renin

IC50: 1.5 nM (renin)[1]; 0.6 nM (human renin), 2 nM (marmoset renin), 80 nM (rat renin), 7 nM (dog renin), 11 nM (rabbit renin), 63 nM (guinea pig renin), 150 nM (pig renin)[2]

Aliskiren hydrochloride inhibits plasma renin activity (PRA) in vitro with IC50s of 2.9 nM (human PRA), 8.0 nM (monkey PRA), respectively[1]. Aliskiren hydrochloride (10 μM; 24 h) inhibits prorenin-induced human aortic smooth muscle cell migration[2]. Aliskiren hydrochloride (1-10 μM; 24 h) inhibits both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity[2]. Cell Migration Assay [2] 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.

Aliskiren hydrochloride (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[3]. Aliskiren hydrochloride (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[4]. Aliskiren hydrochloride (10 mg/kg; p.o.; single dose; 20 d after C26 injection) reduces oxidative stress associated with cancer cachexia[4]. Animal Model: Sodium-depleted marmosets[3] 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[4] 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.

[1]. Yuji Nakamura, et al. Discovery of DS-8108b, a Novel Orally Bioavailable Renin Inhibitor. ACS Med. Chem. Lett., 2012, 3 (9), pp 754–758

[2]. Ferri N, et al. Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration. J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):284-91.

[3]. Wood JM, et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun. 2003 Sep 5;308(4):698-705.

[4]. Wang C, et al. Aliskiren targets multiple systems to alleviate cancer cachexia. Oncol Rep. 2016 Nov;36(5):3014-3022.