Synthesis of selective inhibitors of sphingosine kinase 1

Sphingosine kinase isoform 1 (SK1) inhibitors may serve as therapeutic agents for proliferative diseases, including hypertension. We synthesized a series of sphingosine-based SK1-selective inhibitors, the most potent of which is RB-005 (IC50 = 3.6 mu M), which also induced proteasomal degradation of SK1 in human pulmonary arterial smooth muscle cells.