VTP-27999 (Hydrochloride)

VTP-27999 Hydrochloride is an orally active renin inhibitor. VTP-27999 Hydrochloride functionally inhibits renin and acid-activated prorenin, suppresses plasma renin activity and modulates plasma and urinary aldosterone levels. VTP-27999 Hydrochloride reduces mean arterial blood pressure, induces plasma renin concentration increases, decreases plasma angiotensin II levels and enhances renin immunoreactivity. VTP-27999 (Hydrochloride) can be used for the research of hypertension and chronic renal disease^[1][2][3]. In Vitro:VTP-27999 (Compound 9) Hydrochloride inhibits 0.3 nM purified recombinant human renin in buffer with an IC₅₀ of 0.47 nM^[1].
VTP-27999 Hydrochloride inhibits renin 36 pM purified recombinant human renin in buffer with an IC₅₀ of 0.30 nM^[1].
VTP-27999 Hydrochloride inhibits human plasma renin activity with an IC₅₀ of 1.1 nM^[1].
VTP-27999 Hydrochloride does not inhibit human liver microsomal CYP3A4 with an IC₅₀ greater than 30000 nM^[1].
VTP-27999 (10 μM) Hydrochloride inhibits human β-secretase, cathepsin D, and cathepsin E by less than 10%^[1].
VTP-27999 (0.001-100 μM; 48 h) binds to recombinant human prorenin but does not induce its unfolding^[3].
VTP-27999 (1-300 nM) locks acid-activated recombinant human prorenin in its open conformation with a pIC₅₀ of 8.4 and increases its renin immunoreactivity by 41%^[3].
VTP-27999 (0.001 nM-10 μM) increases recombinant human renin immunoreactivity by 30% to 40% at concentrations ≥10 nM^[3].
VTP-27999 (0.001 nM-10 μM) increases endogenous human plasma renin immunoreactivity by up to 70% (untreated) and 35% (trypsin-activated) at concentrations ≥10 nM^[3]. In Vivo:VTP-27999 (Compound 9) (10 mg/kg; p.o.; single dose) Hydrochloride exhibits superior oral efficacy over Aliskiren (HY-12176) in a double transgenic rat model of hypertension, with a greater reduction in mean arterial blood pressure at 24 hours and a longer duration of action^[1].