司帕生坦 (Filspari)

概览

Sparsentan is an endothelin and angiotensin II receptor antagonist indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression.

作用机制

Sparsentan is a molecule that acts as a dual antagonist of the endothelin type A receptor (ETR) and the angiotensin II (Ang II) type 1 receptor (ATR). It possesses two clinically validated mechanisms of action and selectively blocks the action of two potent vasoconstrictor and mitogenic agents, Ang II and endothelin 1 (ET-1), at their respective receptors. ET-1 and Ang II contribute to the pathogenesis of immunoglobulin A nephropathy (IgAN), a condition characterized by the increased production of galactose-deficient IgA1 (Gd-IgA1) antibodies. Gd-IgA1 antibodies lead to mesangial cell activation and proliferation, which stimulates and is stimulated by ET-1 and Ang II production. The pathological cycle of IgAN results in a compromised glomerular filtration barrier and subsequent proteinuria and haematuria. By acting as both an angiotensin receptor blocker (ARB) and an endothelin receptor antagonist (ERA), sparsentan reduces proteinuria in patients with IgAN. Sparsentan has a high affinity for both ETR (Ki= 12.8 nM) and ATR (Ki=0.36 nM), and greater than 500-fold selectivity for these receptors over the endothelin type B and angiotensin II subtype 2 receptors.

适应症

Sparsentan is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.

• Proteinuria