Fig. 6

TP antagonism using NTP42 alleviates key hallmarks associated with PAH. The thromboxane receptor (TP) is a key driver of pulmonary arterial hypertension (PAH). Signalling through the TP, the cyclooxygenase-derived prostanoid thromboxane (TX) A₂ and free-radical induced isoprostane 8-iso-prostaglandin (PG) F_2α both elicit profound effects that contribute to the pathology of PAH, including vasoconstriction and endothelial and smooth muscle cell hyperproliferation, pulmonary vascular remodelling, inflammation, fibrosis, and thrombosis. Within this preclinical study, NTP42 reduced MCT-induced PAH as determined from the haemodynamic measurements, and at least to a similar extent as the standard-of-care drug Sildenafil or Selexipag. Moreover, NTP42 was superior to Sildenafil and Selexipag in reducing the vascular remodelling, mast cell recruitment and pulmonary collagen deposition in the MCT-treated animals. Based on these findings, blockade of the TP using NTP42 is predicted to alleviate the pathophysiology of PAH, representing a novel therapeutic target with marked benefits over existing therapies