Sparsentan – a dual antagonist – literature
review on endothelin and endothelin antagonists

Sparsentan – a dual antagonist - literature review on endothelin and endothelin antagonists

The endothelin (ET) family consist of three 21 – amino-acid peptides (ET-1, ET-2 and ET-3). The most biologically relevant is ET-1. Endothelin acts by bin- ding to two receptors- ETA and ETB. ET system plays an important role in hu- man physiology by modulating total and regional blood flow, GFR, sodium and water secretion, acid-base handling by the kidneys. The pathologic effects of ET-1 in the kidney are largely mediated by activation of the ETA receptor which promotes renal cell injury, proliferation of mesangial cells, vascular remode- ling, proteinuria, inflammation, hypertrophy and development of renal fibrosis. Endothelin receptor antagonists’ (ERAs) therapeutic potential was studied in many pathological conditions including kidney diseases. Several large studies demonstrated beneficial effects of ERAs in diabetic nephropathy on top of the renin-angiotensin-aldosterone system (RAAS) antagonists. The results of prec- linical and early clinical studies of combined ERA and RAAS inhibitors led to development of a dual antagonist - sparsentan, which is presently evaluated in phase 3 clinical trials.

(NEPHROL DIAL POL. 2021; 25: 77-82)