Substance
ID:73727
Names and Identifiers
IUPAC Traditional name
fumaric acid; bis(tekturna)
IUPAC name
(2E)-but-2-enedioic acid; bis((2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide)
Synonyms
Aliskiren hemifumarate
Registration numbers
CAS Number
Properties
Safety Information
Storage Condition
-20°C
Pharmacology Properties
Target
Renin
Product Information
Salt Data
fumarate
Molecule Details
Research Area
Description
Cardiovascular Disease
Biological Activity
Description
Aliskiren hemifumarate is a direct renin inhibitor with IC50 of 1.5 nM.
Targets
Renin
IC50
1.5 nM [1]
In Vitro
Aliskiren hemifumarate appears to bind to both the hydrophobic S1/S3-binding pocket and to a large, distinct subpocket that extends from the S3-binding site towards the hydrophobic core of renin. Oral bioavailability of Aliskiren hemifumarate is 2.4% in rats, 16% in marmosets and about 2.5% in humans. [2]
In Vivo
Aliskiren hemifumarate (< 10="" mg/kg,="" oral)="" inhibits="" plasma="" renin="" activity="" and="" lowers="" blood="" pressure="" in="" sodium-depleted="" marmosets.="">[3] Once-daily oral treatment with Aliskiren hemifumarate lowers blood pressure effectively, with a safety and tolerability profile, in patients with mild-to-moderate hypertension. [4]
Clinical Trials
Aliskiren hemifumarate is in Phase IV clinical trial of patients with hypertension.
Features
Combination Therapy
Description
The combination of Aliskiren hemifumarate (300 mg) and Valsartan (320 mg) lower mean sitting diastolic blood pressure from baseline by 12? mm Hg, significantly more than either monotherapy. [5]
Protocol
Kinase Assay [1]
Enzyme inhibition assay
All reactions are carried out in a flat bottom black opaque microtiter plate. Aliskiren hemifumarate in DMSO (2 μL) are mixed with 100 μL of the assay buffer (50 mM Tris-HCl (pH7.9), 100 mM NaCl) containing 5 μL of trypsin-activated recombinant human renin (final enzyme concentration of 50 μM), and the solution is pre-incubated at room temperature for 10 min. Next, 2 μM of the substrate (Arg-Glu(EDANS)-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-Lys(DABCYL)-Arg) in 100 μL of the assay buffer is added, and the resulting mixture is incubated at 37 °C for 90 min. After completion of incubation, the concentration of generated angiotensin I is measured by fluorescence at 492 nm (excitation at 340 nm) using a multilabel reader.
Cell Assay []
Animal Study []
Molecular Spectra
No Data Available
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References
• Nakamura Y, et al. ACS Med Chem Lett, 2012, 3(9), 754–758.
• Gradman AH, et al. Circulation, 2005, 111(8), 1012-1018.
• Oparil S, et al. Lancet, 2007, 370(9583), 221-229.
• Wood JM, et al. Biochem Biophys Res Commun, 2003, 308(4), 698-705.
• Buczko W, et al. Pharmacol Rep, 2008, 60(5), 623-631.