Pulmonary arterial hypertension (PAH), characterized by high morbidity and mortality, is a serious hazard to human life. Until now, the long-term survival of the PAH patients is still suboptimal. Recently, sphingosine kinase 1 (SPHK1) has drawn more and more attention due to its essential role in the pulmonary vasoconstriction, remodeling of pulmonary blood vessels and right cardiac lesions in PAH patients, and this enzyme is regarded as a new target for the treatment of PAH. Here, we discussed the multifarious functions of SPHK1 in PAH physiology and pathogenesis. Moreover, the structural features of SPHK1 and binding modes with different inhibitors were summarized. Finally, recent advances in the medicinal chemistry research of SPHK1 inhibitors are presented.
The Sphingosine Kinase 1/Sphingosine-1-Phosphate Pathway in Pulmonary Arterial Hypertension
