SK1-I hydrochloride (BML-258 hydrochloride) is a sphingosine analog that enhances autophagy and exhibits antitumor activity. This isozyme-specific competitive SPHK1 inhibitor has a Ki value of 10 μM [1] [2].

SK1-I hydrochloride (0-10 μM; 24 hours) reduces cancer cell growth and survival in a TP53-dependent manner in HCT116 cells and TP53-null HCT116 cells. Additionally, SK1-I hydrochloride (0-20 μM; 12 hours) increases CASP3 cleavage in TP53-expressing HCT116 cells, indicating apoptosis. [Cell Viability Assay: HCT116 cells and TP53-null HCT116 cells; 0, 2.5, 5, 7.5, 10 μM; 24 hours. Result: Decreased cell growth and survival. Western Blot Analysis: HCT116 cells and TP53-null HCT116 cells; 0, 5, 10, 20 μM; 12 hours. Result: Increased CASP3 cleavage].

Pre-treatment with SK1-I hydrochloride (also known as BML-258 hydrochloride) via intraperitoneal (i.p.) injection at 75 mg/kg, administered 24 hours before baseline mean arterial blood pressure (MAP) measurement, significantly reduces the hypotensive effect of subsequent anandamide administration (i.v. injection at 1 and 10 mg/kg). This was observed in male C57BL/6 mice weighing 24 ± 3.5 g. The regimen highlights the drug's impact on blood pressure modulation and demonstrates a marked decrease in baseline MAP, suggesting a notable interaction between SK1-I hydrochloride and anandamide in vascular responses.