The sphingomyelin pathway is important in cell regulation and determining cellular fate. Inhibition of sphingosine kinase isoform 1 (SK1) within this pathway, leads to a buildup of sphingosine and ceramide, two molecules directly linked to cell apoptosis, while decreasing the intracellular concentration of sphingosine-1-phosphate (S1P), a molecule linked to cellular proliferation. Recently, an inhibitor capable of inhibiting SK1 in vitro was identified, but also shown to be ineffective in vivo. A set of compounds designed to assess the impact of synthetic modifications to the hydroxynaphthalene ring region of the template inhibitor with SK1 to obtain a compound with increased efficacy in vivo. Of these fifteen compounds, 4A was shown to have an IC₅₀ = 6.55 μM with improved solubility and in vivo potential.

鞘磷脂途径在细胞调节和决定细胞命运中很重要。抑制该通路中的鞘氨醇激酶同工型 1 (SK1) 会导致鞘氨醇和神经酰胺的积累，这两种分子与细胞凋亡直接相关，同时降低鞘氨醇-1-磷酸 (S1P) 的细胞内浓度，这是一种与细胞相关的分子增殖。最近，一种能够在体外抑制 SK1 的抑制剂被鉴定出来，但在体内也被证明是无效的。一组化合物，旨在评估用 SK1 对模板抑制剂的羟基萘环区域进行合成修饰的影响，以获得具有更高体内功效的化合物。在这 15 种化合物中，4A 被证明具有 IC₅₀  = 6.55 μM，具有更高的溶解度和体内潜力。