RE 201

Sparsentan (RE-021; BMS-346567; PS433540; DARA-a) is a highly potent dual angiotensin II and endothelin A receptor antagonist with Kis of 0.8 and 9.3 nM, respectively.

Signaling Pathways >> GPCR/G Protein >> Angiotensin Receptor

Signaling Pathways >> GPCR/G Protein >> Endothelin Receptor

Research Areas >> Cardiovascular Disease

Ki: 0.8 nM (Human angiotensin II), 9.3 nM (Human endothelin A), 0.4 nM (Rat angiotensin II)[1]

Sparsentan dose dependently antagonizes the angiotensin II-induced pressor response with an ED50 value of 0.8 µmol/kg iv and 3.6 µmol/kg po. Sparsentan also shows efficacious and long acting in the big ET-1-induced pressor model. Sparsentan causes a significant lowering of blood pressure at the lowest dose tested (10 µmol/kg/day) in spontaneously hypertensive rats. Sparsentan shows good oral bioavailability in rats, dogs, and monkeys, averaging 40%, 86%, and 21% F, respectively. At 100 µmol/kg/day, Sparsentan reduces the blood pressure from 170 to less than 100 mmHg during the course of the drug’s pharmacokinetic duration. Sparsentan at 100 µmol/kg/day essentially converts the spontaneously hypertensive rats into normotensive rats during the course of its pharmacokinetic duration[1].

Rats: Rats are gavaged with vehicle, and immediately thereafter the first bolus (intravenous) iv injection of angiotensin II served as the control pressor response. Irbesartan (30 µmol/kg) and Sparsentan (30 µmol/kg) are given by oral gavage (po), and the rats are re-challenged with angiotensin II at various intervals up to 240 min. There are 6-8 rats per drug dose. The difference between the maximum blood pressure increase before and after drug is reported as the percent (%) inhibition of the angiotensin II pressor effect[1].

[1]. Murugesan N, et al. Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem. 2005 Jan 13;48(1):171-9.

Angiotensin II acetate salt | AVE 0991 | BQ-788 (sodium salt) | Endothelin-1 (human, bovine, dog, mouse, porcine, rat) acetate salt | A 779 | Tranilast | PD123319 di(trifluoroacetate) | Telmisartan | Atrasentan hydrochloride | BQ-123 | Angiotensin II Receptor Ligand | Sacubitril/valsartan (LCZ696) | EMA401 | Fimasartan | Zibotentan (ZD4054)