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| 10mg |
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| 50mg |
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| 100mg |
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Aliskiren D6 hemifumarate is the hexa-deuterated form of Aliskiren hemifumarate ( SPP-100; CGP60536; Rasilez; CGP-60536; Tekturna), which is a direct renin inhibitor approved as an antihypertensive drug.
| ln Vitro |
In vitro, plasma renin activity (PRA) is inhibited by isaliskiren hemifumarate, with an IC50 of 2.9 nM for human PRA and 8.0 nM for monkey PRA [1]. Human aortic smooth muscle cell migration mediated by prorenin is inhibited by isoformaliskiren hemifumarate (5 μM; 24 h) [2]. Aliskiren hemifumarate (1–10 μM; 24 hours) has no discernible effect on PDGF-BB activity, but it suppresses the development of lamellipodia and morphological alterations generated by prorenin [2].
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| ln Vivo |
In sodium-depleted marmosets, aliskiren hemifumarate (3 mg/kg, 10 mg/kg; oral; daily; 0–12 days) suppresses renin and reduces blood pressure without changing heart rate [3]. In mice, aliskiren hemifumarate (10 mg/kg; oral; single dosage) decreases tumors, postpones the onset of cachexia, and increases survival. Moreover, it can boost physical activity, prevent muscle atrophy, and increase general body strength, mobility, and coordination [4]. Twenty days following a C26 injection, a single oral dosage of 10 mg/kg of aliskiren hemifumarate is administered to alleviate oxidative stress linked to cancer cachexia [4].
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: Smooth Muscle Cells (SMC) Tested Concentrations: 1-10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Prorenin (10 nM) at 10 μM inhibits human aortic smooth muscle cell migration. |
| Animal Protocol |
Animal/Disease Models: Sodium-deficient marmoset [3]
Doses: 3 mg/kg, 10 mg/kg Route of Administration: po (oral gavage); one time/day; 12-day Experimental Results: Plasma immunoreactive renin levels increased, blood pressure diminished, and Does not affect heart rate. There was no rebound increase in blood pressure after the end of aliskiren treatment at any dose. Inhibits RAS and controls the upregulation of pro-inflammatory cytokines. Animal/Disease Models: BALB/c mouse cancer cachexia model injected with C26 mouse colon cancer cells [4] Doses: 10 mg/kg Route of Administration: po (oral gavage); 5th day after C26 injection (as a preventive strategy, AP group) or day 12 (as treatment strategy, AT group); C26 20-day post-injection Experimental Results: Enhanced grip strength, coordination, and athletic ability. Suppresses serum Ang I and Ang II levels as well as serum and muscle tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. |
| References |
[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, 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. [5]. Buczko W, et al. Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor. Pharmacol Rep. 2008 Sep-Oct;60(5):623-31. [6]. Gradman AH, et al.Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation, 2005, 111(8), 1012-1018. |
| Molecular Formula |
C₃₂H₄₉D₆N₃O₈
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|---|---|
| Molecular Weight |
615.83
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| CAS # |
173334-58-2
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| Related CAS # |
Aliskiren;173334-57-1;Aliskiren hydrochloride;173399-03-6;Aliskiren-d6 hydrochloride;1246815-96-2;Aliskiren-d6 hemifumarate
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| SMILES |
O=C(O)/C=C/C(O)=O.O=C(NCC(C)(C(N)=O)C)[C@@H](C[C@@H]([C@H](C[C@@H](C(C)C)CC1=CC=C(OC)C(OCCCOC)=C1)N)O)C(C)C.O=C(NCC(C)(C(N)=O)C)[C@H](C(C)C)C[C@H](O)[C@@H](N)C[C@@H](C(C)C)CC2=CC=C(OC)C(OCCCOC)=C2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ≥ 50 mg/mL (~41.00 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (41.00 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6238 mL | 8.1191 mL | 16.2382 mL | |
| 5 mM | 0.3248 mL | 1.6238 mL | 3.2476 mL | |
| 10 mM | 0.1624 mL | 0.8119 mL | 1.6238 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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