Physicochemical Properties
| Molecular Formula | C64H110N6O16 |
| Molecular Weight | 1231.7 |
| Exact Mass | 1218.8 |
| Related CAS # | Aliskiren;173334-57-1;Aliskiren hydrochloride;173399-03-6;Aliskiren-d6 hydrochloride;1246815-96-2;Aliskiren-d6 hemifumarate |
| PubChem CID | 6918427 |
| Appearance | White to off-white solid powder |
| Melting Point | 72-75?C |
| Vapour Pressure | 1.59E-23mmHg at 25°C |
| LogP | 9.881 |
| Hydrogen Bond Donor Count | 10 |
| Hydrogen Bond Acceptor Count | 18 |
| Rotatable Bond Count | 40 |
| Heavy Atom Count | 86 |
| Complexity | 836 |
| Defined Atom Stereocenter Count | 8 |
| SMILES | [2H]C([2H])([2H])C([C@H](C[C@@H]([C@H](C[C@H](CC1=CC(=C(C=C1)OC)OCCCOC)C(C)C)N)O)C(=O)NCC(C)(C)C(=O)N)C([2H])([2H])[2H].[2H]C([2H])([2H])OCCCOC1=C(C=CC(=C1)C[C@@H](C[C@@H]([C@H](C[C@@H](C(C)C)C(=O)NCC(C)(C)C(=O)N)O)N)C(C)C)OC([2H])([2H])[2H].C(=C/C(=O)O)\C(=O)O |
| InChi Key | KLRSDBSKUSSCGU-PFGUTONBSA-N |
| InChi Code | InChI=1S/2C30H53N3O6.C4H4O4/c2*1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36;5-3(6)1-2-4(7)8/h2*10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35);1-2H,(H,5,6)(H,7,8)/b;;2-1+/t2*22-,23-,24-,25-;/m00./s1/i7D3,8D3;3D3,4D3; |
| Chemical Name | (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2-(1,1,1,3,3,3-hexadeuteriopropan-2-yl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methylnonanamide;(2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-8-methyl-2-propan-2-yl-7-[[4-(trideuteriomethoxy)-3-[3-(trideuteriomethoxy)propoxy]phenyl]methyl]nonanamide;(E)-but-2-enedioic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| 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]. |
| 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]. |
| 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]. Discovery of DS-8108b, a Novel Orally Bioavailable Renin Inhibitor. ACS Med. Chem. Lett., 2012, 3 (9), pp 754-758. [2]. Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration. J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):284-91. [3]. Structure-based design of aliskiren, a novel orally effective renin inhibitor.Biochem Biophys Res Commun, 2003, 308(4), 698-705. [4]. Aliskiren targets multiple systems to alleviate cancer cachexia. Oncol Rep. 2016 Nov;36(5):3014-3022. [5]. Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor. Pharmacol Rep. 2008 Sep-Oct;60(5):623-31. [6]. 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. |
| Additional Infomation |
Aliskiren fumarate is the hemifumarate salt of aliskiren. It has a role as an antihypertensive agent. It contains an aliskiren. Aliskiren Hemifumarate is an orally active nonpeptide renin inhibitor with antihypertensive activity. Aliskiren selectively binds to the S3 sub-pocket of renin, an enzyme in the renin-angiotensin-aldosterone system (RAAS) that is responsible for converting angiotensinogen to angiotensin I (AT I). By inhibiting the activity of renin, the conversion to AT I is prevented, which in turn prevents the conversion of AT I to AT II. This prevents arterial vasoconstriction by AT II and inhibits the production of aldosterone by AT II. As aldosterone causes re-uptake of sodium and water and eventually an increase in extracellular volume, aliskiren is able to prevent the effects that contribute to an increase in blood pressure. See also: Aliskiren (has active moiety); Aliskiren hemifumarate; amlodipine besylate (component of); Aliskiren hemifumarate; hydrochlorothiazide (component of) ... View More ... |
Solubility Data
| Solubility (In Vitro) | H2O : ≥ 50 mg/mL (~41.00 mM) |
| 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 | 0.8119 mL | 4.0594 mL | 8.1189 mL | |
| 5 mM | 0.1624 mL | 0.8119 mL | 1.6238 mL | |
| 10 mM | 0.0812 mL | 0.4059 mL | 0.8119 mL |