Aliskiren hemifumarate

2 years -20°C Powder, 2 weeks 4°C in DMSO, 2 months -80°C in DMSO

Aliskiren hemifumarate is in Phase IV clinical trial of patients with hypertension.

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]

Enzyme inhibition assay, All reactions are carried out in a flat bottom black opaque microtiter plate. Aliskiren hemifumarate in DMSO (2 uL) are mixed with 100 uL of the assay buffer (50 mM Tris-HCl (pH7.9), 100 mM NaCl) containing 5 uL of trypsin-activated recombinant human renin (final enzyme concentration of 50 uM), and the solution is pre-incubated at room temperature for 10 min. Next, 2 uM of the substrate (Arg-Glu(EDANS)-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-Lys(DABCYL)-Arg) in 100 uL 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.

Aliskiren hemifumarate is a direct renin inhibitor with IC50 of 1.5 nM.