Sparsentan (RE-021)

Sparsentan is a dual antagonist of angiotensin II type 1 (AT₁) and endothelin receptor type A (ET_A; K_is = 0.8 and 9.3 nM, respectively, for the human receptors).¹ It is selective for these receptors over AT₂ and ET_B receptors (K_is = >10 ?M for both). Sparsentan inhibits angiotensin II-induced pressor responses in conscious normotensive rats (ED₅₀ = 3.6 ?mol/kg, p.o). It reduces mean arterial pressure in spontaneously hypertensive rats when administered orally at doses of 10, 30, or 100 ?mol/kg per day. Dietary administration of sparsentan (1,800 ppm) reduces albuminuria and inhibits development of glomerulosclerosis in the gddY mouse model of IgA nephropathy.²

1.Murugesan, N., Gu, Z., Fadnis, L., et al.Dual angiotensin II and endothelin A receptor antagonists: Synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokineticsJ. Med. Chem.48(1)171-179(2005) 2.Nagasawa, H., Suzuki, H., Jenkinson, C., et al.The dual endothelin ETA and angiotensin AT1 receptor blocker sparsentan protects against the development of albuminuria and glomerulosclerosis in the gddY mouse model of IgANephrol. Dial. Transplant.35(Suppl. 3)P0348(2020)